Addiction biology
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Awareness of cannabis dependence as a clinically relevant issue has grown in recent years. Clinical and laboratory studies demonstrate that chronic marijuana smokers can experience withdrawal symptoms upon cessation of marijuana smoking and have difficulty abstaining from marijuana use. ⋯ The role of the CB1 receptor in the development of marijuana dependence and expression of withdrawal will also be discussed. Lastly, treatment options that may alleviate withdrawal symptoms and promote marijuana abstinence will be considered.
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The identification of the cannabinoid receptor type 1 (CB1 receptor) was the milestone discovery in the elucidation of the behavioural and emotional responses induced by the Cannabis sativa constituent Delta(9)-tetrahydrocannabinol. The subsequent years have established the existence of the endocannabinoid system. The early view relating this system to emotional responses is reflected by the fact that N-arachidonoyl ethanolamine, the pioneer endocannabinoid, was named anandamide after the Sanskrit word 'ananda', meaning 'bliss'. ⋯ Second, it has a wide neuro-anatomical distribution, modulating brain regions with different functions in responses to aversive stimuli. Third, endocannabinoids regulate the release of other neurotransmitters that may have even opposing functions, such as GABA and glutamate. Further understanding of the temporal, spatial and functional characteristics of this system is necessary to clarify its role in emotional responses and will promote advances in its therapeutic exploitation.
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Since the discovery of the endocannabinoid system, a growing body of psychiatric research has emerged focusing on the role of this system in major psychiatric disorders like schizophrenia (SCZ), bipolar disorder (BD), major depression and anxiety disorder. Continuing in the line of earlier epidemiological studies, recent replication studies indicate that frequent cannabis use doubles the risk for psychotic symptoms and SCZ. Further points of clinical research interest are alterations of endocannabinoids and their relation to symptoms as well as postmortem analyses of cannabinoid CB(1) receptor densities in SCZ. ⋯ In addition, prior antipsychotic treatment decreased the numerical density of CB(1) immunoreactive glial cells in bipolar patients. Although the data on the influence of cannabis use on the development of major depression is controversial, cannabinoid compounds could display a new class of medication, as suggested by the antidepressive effects of the fatty acid amino hydrolase inhibitor URB597 in animal models. With numerous open questions and controversial results, further research is required to specify and extend the findings in this area, which provides a promising target for novel pharmacotherapeutic interventions.
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Addiction is a chronic, recurring and complex disorder. It is characterized by anomalous behaviors that are linked to permanent or long-lasting neurobiological alterations. Furthermore, the endocannabinoid system has a crucial role in mediating neurotransmitter release as one of the main neuromodulators of the mammalian central nervous system. ⋯ Specifically, most of the studies relate to the hippocampus and nucleus accumbens. Moreover, the neurotransmitter with the fewest number of related studies is acetylcholine (excepting in the hippocampus), whereas there is a large number that evaluates GABA, glutamate and dopamine. Finally, we propose a possible interpretation of the role of the endocannabinoid system in the phenomenon of addiction.
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A remarkable amount of literature has been generated demonstrating the functional similarities between the endogenous opioid and cannabinoid systems. Anatomical, biochemical and molecular data support the existence of reciprocal interactions between these two systems related to several pharmacological responses including reward, cognitive effects, and the development of tolerance and dependence. However, the assessment of the bidirectionality of these effects has been difficult due to their variety and complexity. ⋯ Cross-tolerance and cross-sensitization, although not always bidirectional, are also supported by a number of evidence, while less data have been gathered regarding the relationship of these systems in cognition and emotion. Nevertheless, the most recent advances in cannabinoid-opioid cross-modulation have been made in the area of drug craving and relapse processes. The present review is focused on the latest developments in the cannabinoid-opioid cross-modulation of their behavioural effects and the possible neurobiological substrates involved.