Differential effects of cannabis exposure during early versus later adolescence on the expression of psychosis in homeless and precariously housed adults.

Longitudinal studies of cannabis exposure during early adolescence in the general population frequently report an increased risk of subsequently developing psychotic symptoms or a psychotic illness. However, there is a dearth of knowledge about the effects of early cannabis exposure on psychosis in homeless and precariously housed adults, who represent a population afflicted with high rates of psychosis. The aim of the present study was to examine how early cannabis exposure (by age 15) compared to later first use (after age 15) affected the expression of adult psychosis in this population. Secondary measures of psychopathology, drug use, cognition and brain structure were also collected. 437 subjects were recruited from single room occupancy hotels in the urban setting of the Downtown Eastside of Vancouver, Canada. Psychiatric diagnoses were determined, and psychotic symptom severity was measured with the 5-factor PANSS. Participants completed a battery of neurocognitive tests, and brain structure was assessed using structural and diffusion tensor imaging MRI scans. Results indicated that early cannabis exposure was associated with an increased risk (OR = 1.09, p < .05) of developing substance induced psychosis, whereas later first use increased risk (OR = 2.19, p < .01) of developing schizophrenia or schizoaffective disorder. There was no group difference in neurocognitive function, although differences were observed in the lateral orbitofrontal cortex and white matter tract diffusivity. These findings indicate that early cannabis exposure in this population may increase the risk of developing drug associated psychoses, which could potentially be mediated in part through altered neurodevelopmental brain changes.

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study.

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.

Comparisons of Voxel-Based Morphometric Brain Volumes of Individuals with Methamphetamine-Induced Psychotic Disorder and Schizophrenia Spectrum Disorder and Healthy Controls.

BACKGROUND: Several psychological and neurological pathways are described to explain the emergence and maintenance of psychiatric disorders, and changes in brain volumes and brain activity are observed as correlates of psychiatric disorders. In the present study, we investigated if and to what extent specific voxel-based morphometric brain volume differences could be observed among individuals with methamphetamine-induced psychosis (MAIP) and schizophrenia spectrum disorder (SSD) compared to healthy controls. METHODS: A total of 69 individuals took part in the present study. Of those, 26 were diagnosed with MAIP, 23 with SSD, and 20 were healthy controls. After a thorough psychiatric assessment, participants underwent brain volume measurement. RESULTS: Compared to healthy controls, participants with MAIP had smaller volumes for left caudate and left and right parahippocampal gyrus. Compared to healthy controls, participants with SSD had smaller volumes for the gray and white matter, left amygdala, left hippocampus, left parahippocampal gyrus, left putamen, and the total volume. Compared to individuals with MAIP, individuals with SSD had a lower white matter brain volume. CONCLUSIONS: The pattern of results suggests that individuals with MAIP and SSD showed specific and regional brain atrophies on the left hemisphere, always compared to healthy controls. Given the cross-sectional design, it remains undisclosed if specific and regional brain atrophies were the cause or the consequence of the psychiatric issues.

Structural, functional, and neurochemical neuroimaging of methamphetamine-associated psychosis: A systematic review.

Methamphetamine is a highly addictive psychostimulant. A subset of methamphetamine users develops methamphetamine-associated psychosis (MAP), which causes poorer prognoses and cognitive function than those with no psychosis (MNP). Comprehensive and integrative summaries of studies utilizing various neuroimaging modalities (structural, functional, and neurochemical) are limited. We conducted a systematic review of literature regarding clinical neuroimaging research published between January 1988 and July 2018 using the PubMed, Web of Science, Scopus, and ScienceDirect databases. Studies comparing the neuroimaging of patients with MAP with healthy controls or patients with MNP or schizophrenia were included to understand the distinct profiles associated with MAP. A total of six structural, three functional, and three neurochemical studies were reviewed. A general trend was identified that showed MAP-related brain alterations were mainly in the frontal lobe (especially the orbitofrontal cortex), striatum, and limbic systems (amygdala and hippocampus). Furthermore, some clinical manifestations, such as the severity of psychotic symptoms and cognitive performance, were correlated with neuroimaging abnormalities. In summary, distinct structural, functional, and neurochemical changes, especially in the frontostriatal circuit and network dynamic systems, play critical roles in the pathophysiology of MAP. Future studies using longitudinal study designs and including individuals with MNP and schizophrenia as controls are warranted.

A comparison of regional brain volumes and white matter connectivity in subjects with stimulant induced psychosis versus schizophrenia.

RATIONALE: Schizophrenia and stimulant-induced psychosis (SIP) represent two different forms of psychotic disorder, with different etiologies. While many of the symptoms of psychosis are common to both disorders, there have been few direct comparisons between these conditions, especially when controlling for stimulant use in individuals with schizophrenia. OBJECTIVES: We directly compared both psychotic disorders with a comprehensive battery of clinical, neurocognitive and neuroanatomical measures. This included one group with SIP (and concurrent stimulant dependence) and two groups with schizophrenia (either with or without concurrent stimulant dependence). METHODS: Ninety-six participants were recruited from a marginalized urban population, which included 39 with SIP (and concurrent stimulant dependence), 18 with schizophrenia (without stimulant dependence), and 39 with schizophrenia (with concurrent stimulant dependence). All subjects had extensive clinical and neurocognitive evaluations, complemented with structural MRI including diffusion tensor imaging (DTI) sequences to determine regional brain volumes and white matter connectivity. RESULTS: Both positive and negative symptoms were greater in the SZ-dependent group than the other two. Neurocognitive function was broadly similar. The structural brain imaging revealed lateralized changes to the left parietal/temporal lobe, in which regional volumes were smaller in the SZ-dependent than the SZ-non-dependent group. DTI analysis indicated extensive decreases in fractional anisotropy, with parallel increases in radial diffusivity, in the SIP group compared to the SZ-dependent group. CONCLUSIONS: These findings reveal both similarities and differences between SIP and schizophrenia. Furthermore, schizophrenia with concurrent stimulant dependence may be associated with a different clinical and neuroanatomical profile as compared to schizophrenia alone.

Microstructural Findings in White Matter Associated with Cannabis and Alcohol Use in Early-Phase Psychosis: A Diffusion Tensor Imaging and Relaxometry Study.

Accumulating evidence suggests that brain white matter (WM) abnormalities may be central to the pathophysiology of psychotic disorders. In addition, there is evidence that cannabis use and alcohol use each is associated with WM abnormalities. However, there are very limited data on the effects of these substances on WM microstructure in patients with psychosis, especially for those at the early phase of illness. This project aimed to examine the impact of cannabis use and alcohol use on WM tissue in early-phase psychosis (EPP). WM was investigated in 21 patients with EPP using diffusion tensor imaging (DTI) and transverse relaxation time of tissue water (T2), with the primary outcomes being mean fractional anisotropy (FA) and T2. DTI analyses were performed at the full-brain level using tract-based spatial statistics with both DTI and T2 analysis done within a WM volume of interest (VOI) implicated in psychosis (containing the left superior longitudinal fasciculus). Our findings revealed that younger age of onset of regular alcohol use (more than one drink per week) was associated with lower FA values in the left thalamic radiation and left parahippocampal and left amygdalar WM. More frequent lifetime cannabis use was correlated with increased mean full-brain FA. There was no significant relationship found between FA and alcohol or cannabis use within the VOI. Relaxometry analysis revealed trend-level evidence of shortened T2 with later onset of regular alcohol use and with more frequent cannabis use. This study provides novel data demonstrating cortical and subcortical WM findings related to alcohol use in EPP and is the first to combine DTI and relaxometry, relating to this patient population.

Changes in Gray Matter Density, Regional Homogeneity, and Functional Connectivity in Methamphetamine-Associated Psychosis: A Resting-State Functional Magnetic Resonance Imaging (fMRI) Study.

BACKGROUND Using regional homogeneity (ReHo) blood oxygen level-dependent functional MR (BOLD-fMRI), we investigated the structural and functional alterations of brain regions among patients with methamphetamine-associated psychosis (MAP). MATERIAL AND METHODS This retrospective study included 17 MAP patients, 16 schizophrenia (SCZ) patients, and 18 healthy controls. Informed consent was obtained from all patients before the clinical assessment, the severity of clinical symptoms was evaluated prior to the fMRI scanning, and then images were acquired and preprocessed after each participant received 6-min fRMI scanning. The participants all underwent BOLD-fMRI scanning. Voxel-based morphometry was used to measure gray matter density (GMD). Resting-state fMRI (rs-fMRI) was conducted to analyze functional MR, ReHo, and functional connectivity (FC). RESULTS GMD analysis results suggest that MAP patients, SCZ patients, and healthy volunteers show different GMDs within different brain regions. Similarly, the ReHo analysis results suggest that MAP patients, SCZ patients, and healthy volunteers have different GMDs within different brain regions. Negative correlations were found between ReHo- and the PANSS-positive scores within the left orbital interior frontal gyrus (L-orb-IFG) of MAP patients. ReHo- and PANSS-negative scores of R-SFG were negatively correlated among SCZ patients. The abnormal FC of R-MFG showed a negative correlation with the PANSS score among MAP patients. CONCLUSIONS The abnormalities in brain structure and FC were associated with the development of MAP.

Cannabis use in early psychosis is associated with reduced glutamate levels in the prefrontal cortex.

RATIONALE: Recent studies have shown that cannabis may disrupt glutamate (Glu) signaling depressing Glu tone in frequent users. Current evidence have also consistently reported lower Glu-levels in various brain regions, particularly in the medial prefrontal cortex (mPFC) of chronic schizophrenia patients, while findings in early psychosis (EP) are not conclusive. Since cannabis may alter Glu synaptic plasticity and its use is a known risk factor for psychosis, studies focusing on Glu signaling in EP with or without a concomitant cannabis-usage seem crucial. OBJECTIVE: We investigate the effect of cannabis use on prefrontal Glu-levels in EP users vs. both EP non-users and healthy controls (HC). METHODS: Magnetic resonance spectroscopy was used to measure [GlumPFC] of 35 EP subjects (18 of whom were cannabis users) and 33 HC. For correlative analysis, neuropsychological performances were scored by the MATRICS-consensus cognitive battery. RESULTS: [GlumPFC] was lower in EP users comparing to both HC and EP non-users (p < 0.001 and p = 0.01, respectively), while no differences were observed between EP non-users and HC. A greater [GlumPFC]-decline with age was observed in EP users (r = -.46; p = 0.04), but not in EP non-users or HC. Among neuropsychological outcomes, working memory was the only domain that differentiates patients depending on their cannabis use, with users having poorer performances. CONCLUSIONS: Cannabis use is associated with reduced prefrontal [GlumPFC] and with a stronger Glu-levels decline with age. Glutamatergic abnormalities might influence the cognitive impairment observed in users and have some relevance for the progression of the disease.

S-Ketamine-Induced NMDA Receptor Blockade during Natural Speech Production and Its Implications for Formal Thought Disorder in Schizophrenia: A Pharmaco-fMRI Study.

Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, crossover, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 min each while BOLD signal changes were acquired with fMRI. As a measure of linguistic demand, the number of words within 20 s epochs was correlated with BOLD responses. Participants developed S-ketamine-induced psychotic symptoms, particularly positive FTD. Ketamine vs placebo was associated with enhanced neural responses in the right middle and inferior temporal gyri. Similar to a previous fMRI study in schizophrenia patients vs healthy controls applying the same design, S-ketamine reversed functional lateralization during speech production in healthy subjects. Results demonstrate an association between glutamatergic imbalance, dysactivations in lateral temporal brain areas, and FTD symptom formation.

Cocaine Abuse, Traumatic Brain Injury, and Preexisting Brain Lesions as Risk Factors for Bupropion-Associated Psychosis.

BACKGROUND AND OBJECTIVE: Bupropion is generally considered safe and is widely used both as a monotherapy and as an augmentation agent for the treatment of major depression. Concerns have been raised about bupropion's propensity to precipitate new psychosis and worsen existing psychotic symptoms, although the mechanism is poorly understood. Three cases are reported in which bupropion use was associated with psychosis. The aim of the study was to explore the risk factors and possible mechanisms of psychosis in each case. CASE REPORTS: Case 1 describes the interaction of cocaine abuse sensitization in a patient who developed psychosis with a lower dosage of bupropion. Cases 2 and 3 discuss the role of traumatic brain injury and structural brain lesions in increasing the risk of psychosis when using bupropion. CONCLUSIONS: Cocaine abuse, traumatic brain injury, and preexisting brain lesions appear to be risk factors for developing psychosis in persons taking bupropion. In such cases, clinicians should carefully assess the risks and benefits and closely monitor patients for symptoms of psychosis.

Cannabis-associated psychosis: Neural substrate and clinical impact.

Prospective epidemiological studies have consistently demonstrated that cannabis use is associated with an increased subsequent risk of both psychotic symptoms and schizophrenia-like psychoses. Early onset of use, daily use of high-potency cannabis, and synthetic cannabinoids carry the greatest risk. The risk-increasing effects are not explained by shared genetic predisposition between schizophrenia and cannabis use. Experimental studies in healthy humans show that cannabis and its active ingredient, delta-9-tetrahydrocannabinol (THC), can produce transient, dose-dependent, psychotic symptoms, as well as an array of psychosis-relevant behavioral, cognitive and psychophysiological effects; the psychotogenic effects can be ameliorated by cannabidiol (CBD). Findings from structural imaging studies in cannabis users have been inconsistent but functional MRI studies have linked the psychotomimetic and cognitive effects of THC to activation in brain regions implicated in psychosis. Human PET studies have shown that acute administration of THC weakly releases dopamine in the striatum but that chronic users are characterised by low striatal dopamine. We are beginning to understand how cannabis use impacts on the endocannabinoid system but there is much still to learn about the biological mechanisms underlying how cannabis increases risk of psychosis. This article is part of the Special Issue entitled "A New Dawn in Cannabinoid Neurobiology".

Salience attribution and its relationship to cannabis-induced psychotic symptoms.

BACKGROUND: Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity. METHOD: We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant K i cer , was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography. RESULTS: There was no significant difference in aberrant salience between the groups [F 1,32 = 1.12, p = 0.30 (implicit); F 1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F 1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = -0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = -2.05, p = 0.04). CONCLUSIONS: Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.

Subcortical grey matter alterations in cocaine dependent individuals with substance-induced psychosis compared to non-psychotic cocaine users.

After prolonged psychostimulant abuse, transient psychotic symptoms referred to as "substance-induced psychosis" (SIP) can develop - closely resembling symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and schizophrenias suggests that similar underlying neural deficits may contribute to the expression of psychosis across these disorders. To date, neuroanatomical characterization of grey matter structural alterations in SIP has been limited to methamphetamine associated psychosis, with no studies controlling for potential neurotoxic effects of the psychostimulant that precipitates psychosis. To investigate grey matter subcortical alterations in SIP, a voxel-based analysis of magnetic resonance images (MRI) was performed between a group of 74 cocaine dependent nonpsychotic individuals and a group of 29 individuals with cocaine-associated psychosis. The cocaine-associated psychosis group had significantly smaller volumes of the thalamus and left hippocampus, controlling for age, total brain volume, current methamphetamine dependence, and current marijuana dependence. No differences were present in bilateral caudate structures. The findings of reduced thalamic and hippocampal volumes agree with previous reports in the schizophrenia literature, suggesting alterations of these structures are not specific to schizophrenia, but may be common to multiple forms of psychosis.

White matter microstructure and impulsivity in methamphetamine dependence with and without a history of psychosis.

BACKGROUND: Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). METHODS: Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial (λ‖ ) and radial diffusivity (λ⊥ ), and their association with impulsivity scores and psychotic symptoms. RESULTS: The MAP group displayed widespread higher MD, λ‖ and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. CONCLUSIONS: MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc.

Dopaminergic function in cannabis users and its relationship to cannabis-induced psychotic symptoms.

BACKGROUND: Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function. METHODS: We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant [Formula: see text] ) was measured with positron emission tomography and 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine ([(18)F]-DOPA). RESULTS: Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = -.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19). CONCLUSIONS: These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.

[Minocycline as a therapeutic drug for methamphetamine use disorders].

Use of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) is an extremely serious and growing problem throughout the world, including Japan. Antipsychotic drugs have been used for psychotic symptoms associated with these abused drugs. However, there are currently no particular pharmacological treatments for the wide range of symptoms associated with these abused drugs. Recently, we reported that the second generation antibiotic drug minocycline can attenuate behavioral abnormalities and neurotoxicity in the brain after administration of methamphetamine or MDMA. In this review, we discuss minocycline as a new potential therapeutic drug for schizophrenia as well as psychosis associated with these abused drugs.

Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy: a [(123)I]CNS-1261 SPET study.

RATIONALE: Ketamine induces effects resembling both positive and negative psychotic symptoms of schizophrenia. These are thought to arise through its action as an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. OBJECTIVES: We used [(123)I]CNS-1261 to study ketamine binding to NMDA receptors in healthy human controls in vivo and its relationship to positive and negative psychotic symptom induction. MATERIALS AND METHODS: Ten healthy controls underwent two single-photon emission tomography scans with [(123)I]CNS-1261. On each occasion, they received a bolus infusion of either ketamine or saline. The Brief Psychiatric Rating Scale (BPRS) was administered at the end of each scan. Predefined regions of interest were used to estimate change in volume of distribution of [(123)I]CNS-1261 following ketamine administration. Two normalised-to-cortex binding indices were also used in order to study effects of ketamine on NMDA receptor availability by region, after correction for global and nonspecific effects. RESULTS: Ketamine-induced reduction in [(123)I]CNS-1261 volume of distribution in all regions showed the strongest correlation with BPRS negative subscale (p < 0.01). With the normalised-to-cortex measures, NMDA receptor binding in middle inferior frontal cortex showed a significant correlation with BPRS negative subscale (BI1 r = 0.88, BI2 r = 95.9, p < 0.001). CONCLUSIONS: [(123)I]CNS-1261 binding was modulated by ketamine, a drug known to compete for the same site on the NMDA receptor in vitro. Ketamine may induce negative symptoms through direct inhibition of the NMDA receptor, and positive symptoms may arise through a different neurochemical pathway.

Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms.

OBJECTIVE: The authors examined dopamine transporter density in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in methamphetamine users and assessed the relationship of these measures to the subjects' clinical characteristics. METHOD: Positron emission tomography with [(11)C]WIN 35,428 was used to examine the regions of interest in 11 methamphetamine users and nine healthy comparison subjects. Psychiatric symptoms were evaluated with the Brief Psychiatric Rating Scale. RESULTS: Dopamine transporter density in the three regions studied was significantly lower in the methamphetamine users than in the comparison subjects. The lower dopamine transporter density in the orbitofrontal and dorsolateral prefrontal cortex was significantly correlated with the duration of methamphetamine use and the severity of psychiatric symptoms. CONCLUSIONS: Chronic methamphetamine use may cause dopamine transporter reduction in the orbitofrontal cortex, dorsolateral prefrontal cortex, and amygdala in the brain. Psychiatric symptoms in methamphetamine users may be attributable to the decrease in dopamine transporter density in the orbitofrontal cortex and the dorsolateral prefrontal cortex.

Cannabis induced dopamine release: an in-vivo SPECT study.

In a research study aimed at examining the alterations in dopaminergic function in schizophrenia, the authors identified a surreptitious case scenario which provided new insights into the subjective and neurochemical effects of cannabis. A 38-year-old drug-free schizophrenic patient took part in a single photon emission computerized tomographic (SPECT) study of the brain, and smoked cannabis secretively during a pause in the course of an imaging session. Cannabis had an immediate calming effect, followed by a worsening of psychotic symptoms a few hours later. A comparison of the two sets of images, obtained before and immediately after smoking cannabis, indicated a 20% decrease in the striatal dopamine D2 receptor binding ratio, suggestive of increased synaptic dopaminergic activity. This observation offers a plausible biological explanation for the psychotogenic effects of cannabis in vulnerable individuals, and also raises speculations about an interaction between cannabinoid and dopaminergic systems in the brain reward pathways.