Biological psychiatry
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Some of the most compelling evidence supporting an association between cannabinoid agonists and psychosis comes from controlled laboratory studies in humans. Randomized, double-blind, placebo-controlled, crossover laboratory studies demonstrate that cannabinoid agonists, including phytocannabinoids and synthetic cannabinoids, produce a wide range of positive, negative, and cognitive symptoms and psychophysiologic deficits in healthy human subjects that resemble the phenomenology of schizophrenia. These effects are time locked to drug administration, are dose related, and are transient and rarely necessitate intervention. ⋯ Emerging evidence suggests that polymorphisms of several genes related to dopamine metabolism (e.g., COMT, DAT1, and AKT1) may moderate the effects of cannabinoid agonists in laboratory studies. Cannabinoid agonists induce dopamine release, although the magnitude of release does not appear to be commensurate to the magnitude and spectrum of their acute psychotomimetic effects. Interactions between the endocannabinoid, gamma-aminobutyric acid, and glutamate systems and their individual and interactive effects on neural oscillations provide a plausible mechanism underlying the psychotomimetic effects of cannabinoids.
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Biological psychiatry · Apr 2016
ReviewThe Role of Cannabinoids in Neuroanatomic Alterations in Cannabis Users.
The past few decades have seen a marked change in the composition of commonly smoked cannabis. These changes primarily involve an increase of the psychoactive compound ∆(9)-tetrahydrocannabinol (THC) and a decrease of the potentially therapeutic compound cannabidiol (CBD). This altered composition of cannabis may be linked to persistent neuroanatomic alterations typically seen in regular cannabis users. ⋯ Methodologic differences in the quantification of levels of cannabis use prevent accurate assessment of cannabis exposure and direct comparison of findings across studies. Consequently, the field lacks large "consortium-style" data sets that can be used to develop reliable neurobiological models of cannabis-related harm, recovery, and protection. To move the field forward, we encourage a coordinated approach and suggest the urgent development of consensus-based guidelines to accurately and comprehensively quantify cannabis use and exposure in human studies.
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Biological psychiatry · Jan 2016
ReviewHow Preclinical Models Evolved to Resemble the Diagnostic Criteria of Drug Addiction.
Drug addiction is a complex neuropsychiatric disorder that affects a subset of the individuals who take drugs. It is characterized by maladaptive drug-seeking habits that are maintained despite adverse consequences and intense drug craving. ⋯ It is hoped that these new models will increase our understanding of the complex neurobiological mechanisms whereby some individuals switch from controlled drug use to compulsive drug-seeking habits and relapse to these maladaptive habits. Additionally, by paving the way to bridge the gap that exists between biobehavioral research on addiction and the human situation, these models may provide new perspectives for the development of novel and effective therapeutic strategies for drug addiction.
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Biological psychiatry · Aug 2015
ReviewPituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies.
The maladaptive expression and function of several stress-associated hormones have been implicated in pathological stress and anxiety-related disorders. Among these, recent evidence has suggested that pituitary adenylate cyclase activating polypeptide (PACAP) has critical roles in central neurocircuits mediating stress-related emotional behaviors. ⋯ We include our work implicating PACAP signaling within the bed nucleus of the stria terminalis in mediating the consequences of stressor exposure and relatedly, describe more recent studies suggesting that PACAP in the central nucleus of the amygdala may impact the emotional aspects of chronic pain states. In aggregate, these results are consistent with data suggesting that PACAP dysregulation is associated with posttraumatic stress disorder in humans.
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Biological psychiatry · Jun 2015
ReviewMultimodal approaches to define network oscillations in depression.
The renaissance in the use of encephalography-based research methods to probe the pathophysiology of neuropsychiatric disorders is well afoot and continues to advance. Building on the platform of neuroimaging evidence on brain circuit models, magnetoencephalography, scalp electroencephalography, and even invasive electroencephalography are now being used to characterize brain network dysfunctions that underlie major depressive disorder using brain oscillation measurements and associated treatment responses. ⋯ Such goals have been facilitated by the ongoing testing of novel invasive neuromodulation therapies, notably, deep brain stimulation, where clinically relevant treatment effects can be monitored at multiple brain sites in a time-locked causal manner. We review key brain rhythms identified in major depressive disorder as foundation for development of putative biomarkers for objectively evaluating neuromodulation success and for guiding deep brain stimulation or other target-based neuromodulation strategies for treatment-resistant depression patients.