Journal of Clinical Medicine

Editorial

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Open AccessEditorial

Comments from the Editors on the Special Issue “Assessment and Treatment of Addictions: New Tools for Old Problems”

by Pablo Barrio, Laia Miquel and Antoni Gual

J. Clin. Med. 2019, 8(10), 1717; https://doi.org/10.3390/jcm8101717 - 17 Oct 2019

Viewed by 1920

Abstract

New conceptual and technological solutions have been proposed to solve addictive disorders and will be presented in the future. In this Special Issue, we present some of the new assessment tools and treatment options for internet addiction, alcohol, cannabis, cocaine, and gambling disorders. [...] Read more.

New conceptual and technological solutions have been proposed to solve addictive disorders and will be presented in the future. In this Special Issue, we present some of the new assessment tools and treatment options for internet addiction, alcohol, cannabis, cocaine, and gambling disorders. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

Research

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14 pages, 2273 KiB

Open AccessArticle

Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers: Behavioral, Neural and Polygenic Correlates

by Maria Garbusow, Stephan Nebe, Christian Sommer, Sören Kuitunen-Paul, Miriam Sebold, Daniel J. Schad, Eva Friedel, Ilya M. Veer, Hans-Ulrich Wittchen, Michael A. Rapp, Stephan Ripke, Henrik Walter, Quentin J. M. Huys, Florian Schlagenhauf, Michael N. Smolka and Andreas Heinz

J. Clin. Med. 2019, 8(8), 1188; https://doi.org/10.3390/jcm8081188 - 08 Aug 2019

Cited by 20 | Viewed by 4071

Abstract

In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and [...] Read more.

In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, p_SVC = 0.04, x = 26, y = −6, z = −12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (r_s = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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15 pages, 1489 KiB

Open AccessArticle

Cue-Elicited Anxiety and Alcohol Craving as Indicators of the Validity of ALCO-VR Software: A Virtual Reality Study

by Alexandra Ghiţă, Olga Hernández-Serrano, Yolanda Fernández-Ruiz, Miquel Monras, Lluisa Ortega, Silvia Mondon, Lidia Teixidor, Antoni Gual, Bruno Porras-García, Marta Ferrer-García and José Gutiérrez-Maldonado

J. Clin. Med. 2019, 8(8), 1153; https://doi.org/10.3390/jcm8081153 - 02 Aug 2019

Cited by 17 | Viewed by 4142

Abstract

Background: This study is part of a larger project aiming to develop a virtual reality (VR) software to be implemented as a clinical tool for patients diagnosed with alcohol use disorder (AUD). The study is based on previous research in which we identified [...] Read more.

Background: This study is part of a larger project aiming to develop a virtual reality (VR) software to be implemented as a clinical tool for patients diagnosed with alcohol use disorder (AUD). The study is based on previous research in which we identified factors that elicit craving for alcohol in a sample of AUD patients, and which led to the development of a virtual reality software to be used in cue exposure treatments of alcohol use disorder (ALCO-VR). The main objective of this study was to test the effectiveness of ALCO-VR to elicit cue-induced craving and anxiety responses among social drinkers (SD) and AUD patients. Our secondary objective was to explore which responses (cue-induced craving or anxiety) can best differentiate between AUD patients and the SD group. Method: Twenty-seven individuals (13 AUD patients and 14 SD) participated in this study after giving written informed consent. Their anxiety and alcohol craving levels were measured by different instruments at different stages of the procedure. The VR equipment consisted of Oculus Rift technology, and the software consisted of the ALCO-VR platform. Results: Our data indicate that the ALCO-VR software can elicit responses of anxiety and alcohol craving, especially in the group of AUD patients. The cue-induced anxiety response differentiated AUD patients and the SD group better than the cue-induced craving response. Conclusions: The general interest in applying new technologies to the assessment and treatment of mental health disorders has led to the development of immersive real-life simulations based on the advantages of VR technology. Our study concluded that the ALCO-VR software can elicit anxiety and craving responses and that cue-induced anxiety responses can distinguish between AUD and SD groups better than cue-induced craving. The data on craving and anxiety were assessed consistently by different instruments. In addition, we consider that ALCO-VR is able to ecologically assess cue-induced anxiety and alcohol craving levels during exposure to VR alcohol-related environments. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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11 pages, 828 KiB

Open AccessArticle

Motor Adaptation Impairment in Chronic Cannabis Users Assessed by a Visuomotor Rotation Task

by Ivan Herreros, Laia Miquel, Chrysanthi Blithikioti, Laura Nuño, Belen Rubio Ballester, Klaudia Grechuta, Antoni Gual, Mercè Balcells-Oliveró and Paul Verschure

J. Clin. Med. 2019, 8(7), 1049; https://doi.org/10.3390/jcm8071049 - 18 Jul 2019

Cited by 8 | Viewed by 5739

Abstract

Background—The cerebellum has been recently suggested as an important player in the addiction brain circuit. Cannabis is one of the most used drugs worldwide, and its long-term effects on the central nervous system are not fully understood. No valid clinical evaluations of cannabis [...] Read more.

Background—The cerebellum has been recently suggested as an important player in the addiction brain circuit. Cannabis is one of the most used drugs worldwide, and its long-term effects on the central nervous system are not fully understood. No valid clinical evaluations of cannabis impact on the brain are available today. The cerebellum is expected to be one of the brain structures that are highly affected by prolonged exposure to cannabis, due to its high density in endocannabinoid receptors. We aim to use a motor adaptation paradigm to indirectly assess cerebellar function in chronic cannabis users (CCUs). Methods—We used a visuomotor rotation (VMR) task that probes a putatively-cerebellar implicit motor adaptation process together with the learning and execution of an explicit aiming rule. We conducted a case-control study, recruiting 18 CCUs and 18 age-matched healthy controls. Our main measure was the angular aiming error. Results—Our results show that CCUs have impaired implicit motor adaptation, as they showed a smaller rate of adaptation compared with healthy controls (drift rate: 19.3 +/− 6.8° vs. 27.4 +/− 11.6°; t(26) = −2.1, p = 0.048, Cohen’s d = −0.8, 95% CI = (−1.7, −0.15)). Conclusions—We suggest that a visuomotor rotation task might be the first step towards developing a useful tool for the detection of alterations in implicit learning among cannabis users. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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7 pages, 390 KiB

Open AccessArticle

What Do Real Alcohol Outpatients Expect about Alcohol Transdermal Sensors?

by Pablo Barrio, Lidia Teixidor, Magalí Andreu and Antoni Gual

J. Clin. Med. 2019, 8(6), 795; https://doi.org/10.3390/jcm8060795 - 05 Jun 2019

Cited by 2 | Viewed by 2026

Abstract

Objective: Little is known about the potential acceptability of alcohol transdermal sensors among alcohol-dependent outpatients in routine clinical settings. The aim of the present study was to investigate patients’ attitudes towards alcohol transdermal sensors, as well as features associated with enhanced acceptability and [...] Read more.

Objective: Little is known about the potential acceptability of alcohol transdermal sensors among alcohol-dependent outpatients in routine clinical settings. The aim of the present study was to investigate patients’ attitudes towards alcohol transdermal sensors, as well as features associated with enhanced acceptability and usability. Methods: A cross-sectional survey among routine alcohol outpatients was conducted. The Drug Attitude Inventory (DAI-10) was adapted to the field of alcohol transdermal sensors for attitudes assessment. Likert-type and multiple-choice questions were used for acceptability and usability evaluation. Results: 68 patients completed the questionnaire, and the DAI-10 mean score was 3 (standard deviation (SD) = 6.5). Internal consistency revealed a Cronbach alpha of 0.613. The score of a single The score of a single Likert-type question about overall perceived value was 7.4 (SD = 2.6). Its correlation with mean DAI-10 scores was r = 0.633, with p < 0.001. Relapse prevention and a stricter treatment control from therapists were the main reported advantages. Perceived stigma was the main disadvantage. Features increasing device discretion would enhance its acceptability. Conclusions: The data suggest that transdermal sensors could play a role in the clinical treatment of alcohol outpatients and concerns regarding stigma should be taken into account. Future designs should try to minimize size and visibility and stigma concerns should be discussed with patients. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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9 pages, 474 KiB

Open AccessArticle

Clinical Improvements in Comorbid Gambling/Cocaine Use Disorder (GD/CUD) Patients Undergoing Repetitive Transcranial Magnetic Stimulation (rTMS)

by Stefano Cardullo, Luis Javier Gomez Perez, Linda Marconi, Alberto Terraneo, Luigi Gallimberti, Antonello Bonci and Graziella Madeo

J. Clin. Med. 2019, 8(6), 768; https://doi.org/10.3390/jcm8060768 - 30 May 2019

Cited by 13 | Viewed by 4916

Abstract

(1) Background: Pathological gambling behaviors may coexist with cocaine use disorder (CUD), underlying common pathogenic mechanisms. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a therapeutic intervention for CUD. In this case series, we evaluated the clinical effects of rTMS protocol stimulating [...] Read more.

(1) Background: Pathological gambling behaviors may coexist with cocaine use disorder (CUD), underlying common pathogenic mechanisms. Repetitive transcranial magnetic stimulation (rTMS) has shown promise as a therapeutic intervention for CUD. In this case series, we evaluated the clinical effects of rTMS protocol stimulating the left dorsolateral prefrontal cortex (DLPFC) on the pattern of gambling and cocaine use. (2) Methods: Gambling severity, craving for cocaine, sleep, and other negative affect symptoms were recorded in seven patients with a diagnosis of gambling disorder (South Oaks Gambling Screen (SOGS) >5), in comorbidity with CUD, using the following scales: Gambling-Symptom Assessment Scale (G-SAS), Cocaine Craving Questionnaire (CCQ), Beck Depression Inventory-II (BDI-II), Self-rating Anxiety Scale (SAS), and Symptoms checklist-90 (SCL-90). The measures were assessed before the rTMS treatment and after 5, 30, and 60 days of treatment. Patterns of gambling and cocaine use were assessed by self-report and regular urine screens. (3) Results: Gambling severity at baseline ranged from mild to severe (mean ± Standard Error of the Mean (SEM), G-SAS score baseline: 24.42 ± 2.79). G-SAS scores significantly improved after treatment (G-SAS score Day 60: 2.66 ± 1.08). Compared to baseline, consistent improvements were significantly seen in craving for cocaine and in negative-affect symptoms. (4) Conclusions: The present findings provide unprecedent insights into the potential role of rTMS as a therapeutic intervention for reducing both gambling and cocaine use in patients with a dual diagnosis. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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7 pages, 568 KiB

Open AccessArticle

The More You Take It, the Better It Works: Six-Month Results of a Nalmefene Phase-IV Trial

by Pablo Barrio, Carlos Roncero, Lluisa Ortega, Josep Guardia, Lara Yuguero and Antoni Gual

J. Clin. Med. 2019, 8(4), 471; https://doi.org/10.3390/jcm8040471 - 06 Apr 2019

Cited by 3 | Viewed by 2549

Abstract

Background: Alcohol use disorders remain a major health problem. Reduced drinking has been increasingly recognized as a valuable alternative to abstinence. Nalmefene has shown in previous, experimental studies to be a useful tool to aid reduced drinking. However, more data from routine practice [...] Read more.

Background: Alcohol use disorders remain a major health problem. Reduced drinking has been increasingly recognized as a valuable alternative to abstinence. Nalmefene has shown in previous, experimental studies to be a useful tool to aid reduced drinking. However, more data from routine practice settings are needed in order to obtain evidence with high external validity. The aim of this study was to conduct a single-arm phase-IV study with alcohol-dependent outpatients starting with nalmefene for the first time. Here, we present the main effectiveness analysis, scheduled at six months. Methods: This was an observational, multisite, single-arm, phase-IV study conducted among adult alcohol-dependent outpatients who received nalmefene for the first time. The study consisted of four visits: Baseline, 1 month, 6 months, and 12 months. At each visit, drinking variables were obtained from the time-line follow-back regarding the previous month. Satisfaction with medication was also assessed from both patients and professionals with the Medication Satisfaction Questionnaire. A repeated measures mixed model was performed for effective analysis regarding drinking outcomes (reduction in total alcohol consumption and the number of heavy drinking days). Regression analyses were performed in order to find predictors of responses to nalmefene. Results: From a total of 110 patients included, 63 reported data at the six-month visit. On average, patients took nalmefene 69% of days during the month previous to the 6-month assessment. Compared to the one month results, the number of heavy drinking days and total alcohol consumption increased. Still, they were significantly lower than baseline values (outcome evolution over time was from 13.5 to 6.8 to 9.4 days/month, and from 169 to 79 to 116 units/month). A total of 23 patients were considered medication responders. The number of days of taking nalmefene was significantly associated in the regression analysis. Satisfaction was globally high for both professionals and patients and, overall, nalmefene was well-tolerated with no serious adverse events reported. Conclusion: The data provided by this phase-IV study suggest that nalmefene is an effective, well-tolerated treatment for alcohol-dependence in real world, clinical settings. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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12 pages, 651 KiB

Open AccessArticle

Application of Diagnostic Interview for Internet Addiction (DIA) in Clinical Practice for Korean Adolescents

by Hyera Ryu, Ji Yoon Lee, A Ruem Choi, Sun Ju Chung, Minkyung Park, Soo-Young Bhang, Jun-Gun Kwon, Yong-Sil Kweon and Jung-Seok Choi

J. Clin. Med. 2019, 8(2), 202; https://doi.org/10.3390/jcm8020202 - 06 Feb 2019

Cited by 19 | Viewed by 5202

Abstract

The increased prevalence of Internet Gaming Disorder (IGD) and the inclusion of IGD in DSM-5 and ICD-11 emphasizes the importance of measuring and describing the IGD symptoms. We examined the psychometric properties of the Diagnostic Interview for Internet Addiction (DIA), a semi-structured diagnostic [...] Read more.

The increased prevalence of Internet Gaming Disorder (IGD) and the inclusion of IGD in DSM-5 and ICD-11 emphasizes the importance of measuring and describing the IGD symptoms. We examined the psychometric properties of the Diagnostic Interview for Internet Addiction (DIA), a semi-structured diagnostic interview tool for IGD, and verified the application of DIA in clinical practice for Korean adolescents. The DIA is conducted in a manner that interviews both adolescents and their caregivers, and each item has a standardized representative question and various examples. It consists of 10 items based on the DSM-5 IGD diagnostic criteria, which is cognitive salience, withdrawal, tolerance, difficulty in regulating use, loss of interest in other activities, persistent use despite negative results, deception regarding Internet/games/SNS use, use of Internet/games/SNS to avoid negative feelings, interference with role performance, and craving. The study included 103 adolescents divided into three subgroups (mild risk, moderate risk, and addicted group) based on the total score of DIA. Demographic and clinical characteristics were compared among the DIA subgroups using the chi-square test and analysis of variance (ANOVA), and correlation analysis was used to examine the associations of IGD symptoms with clinical variables (e.g., impulsivity, aggression, depression, anxiety, self-esteem). The DIA total score was significantly correlated with Internet and smartphone addiction, depression, state anxiety, self-esteem, impulsivity, aggression, and stress. Furthermore, the moderate risk and addicted group showed significantly higher levels of Internet and smartphone addiction, anxiety, depression, impulsivity, aggression, stress, and lower self-esteem compared with the mild risk group. The Junior Temperament and Character Inventory (JTCI), which measures temperament and character traits, revealed that the mild risk group had higher levels of persistence and self-directedness than did the addicted group. Our findings confirmed the psychometric properties of DIA and the application of the DIA classifications in Korean adolescents. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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15 pages, 508 KiB

Open AccessArticle

A New Measure for Assessing the Intensity of Addiction Memory in Illicit Drug Users: The Addiction Memory Intensity Scale

by Jia-yan Chen, Jie-pin Cao, Yun-cui Wang, Shuai-qi Li and Zeng-zhen Wang

J. Clin. Med. 2018, 7(12), 467; https://doi.org/10.3390/jcm7120467 - 22 Nov 2018

Cited by 5 | Viewed by 3908

Abstract

Disrupting the process of memory reconsolidation could be a promising treatment for addiction. However, its application may be constrained by the intensity of addiction memory. This study aimed to develop and initially validate a new measure, the Addiction Memory Intensity Scale (AMIS), for [...] Read more.

Disrupting the process of memory reconsolidation could be a promising treatment for addiction. However, its application may be constrained by the intensity of addiction memory. This study aimed to develop and initially validate a new measure, the Addiction Memory Intensity Scale (AMIS), for assessing the intensity of addiction memory in illicit drug users. Two studies were conducted in China for item analysis (n = 345) and initial validation (n = 1550) of the AMIS. The nine-item AMIS was found to have two factors (labelled Visual Clarity and Other Sensory Intensity), which accounted for 64.11% of the total variance. The two-factor structure provided a reasonable fit for sample data and was invariant across groups of different genders and different primary drugs of use. Significant correlations were found between scores on the AMIS and the measures of craving. The AMIS and its factors showed good internal consistency (Cronbach’s α: 0.72–0.89) and test-retest reliability (r: 0.72–0.80). These results suggest that the AMIS, which demonstrates an advantage as it is brief and easy to administer, is a reliable and valid tool for measuring the intensity of addiction memory in illicit drug users, and has the potential to be useful in future clinical research. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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Review

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33 pages, 5637 KiB

Open AccessReview

Neurocircuitry of Reward and Addiction: Potential Impact of Dopamine–Glutamate Co-release as Future Target in Substance Use Disorder

by Zisis Bimpisidis and Åsa Wallén-Mackenzie

J. Clin. Med. 2019, 8(11), 1887; https://doi.org/10.3390/jcm8111887 - 06 Nov 2019

Cited by 11 | Viewed by 6157

Abstract

Dopamine–glutamate co-release is a unique property of midbrain neurons primarily located in the ventral tegmental area (VTA). Dopamine neurons of the VTA are important for behavioral regulation in response to rewarding substances, including natural rewards and addictive drugs. The impact of glutamate co-release [...] Read more.

Dopamine–glutamate co-release is a unique property of midbrain neurons primarily located in the ventral tegmental area (VTA). Dopamine neurons of the VTA are important for behavioral regulation in response to rewarding substances, including natural rewards and addictive drugs. The impact of glutamate co-release on behaviors regulated by VTA dopamine neurons has been challenging to probe due to lack of selective methodology. However, several studies implementing conditional knockout and optogenetics technologies in transgenic mice have during the past decade pointed towards a role for glutamate co-release in multiple physiological and behavioral processes of importance to substance use and abuse. In this review, we discuss these studies to highlight findings that may be critical when considering mechanisms of importance for prevention and treatment of substance abuse. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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9 pages, 657 KiB

Open AccessReview

Addiction as Learned Behavior Patterns

by Andreas Heinz, Anne Beck, Melissa Gül Halil, Maximilian Pilhatsch, Michael N. Smolka and Shuyan Liu

J. Clin. Med. 2019, 8(8), 1086; https://doi.org/10.3390/jcm8081086 - 24 Jul 2019

Cited by 31 | Viewed by 8702

Abstract

Individuals with substance use disorders (SUDs) have to cope with drug-related cues and contexts which can affect instrumental drug seeking, as shown with Pavlovian-to-instrumental transfer (PIT) tasks among humans and animals. Our review addresses two potential mechanisms that may contribute to habitual or [...] Read more.

Individuals with substance use disorders (SUDs) have to cope with drug-related cues and contexts which can affect instrumental drug seeking, as shown with Pavlovian-to-instrumental transfer (PIT) tasks among humans and animals. Our review addresses two potential mechanisms that may contribute to habitual or even compulsive drug seeking and taking. One mechanism is represented by Pavlovian and PIT effects on drug intake. The other is a shift from goal-directed to habitual drug intake, which can be accessed via model-based versus model-free decision-making in respective learning tasks. We discuss the impact of these learning mechanisms on drug consumption. First, we describe how Pavlovian and instrumental learning mechanisms interact in drug addiction. Secondly, we address the effects of acute and chronic stress exposure on behavioral and neural PIT effects in alcohol use disorder (AUD). Thirdly, we discuss how these learning mechanisms and their respective neurobiological correlates can contribute to losing versus regaining control over drug intake. Utilizing mobile technology (mobile applications on smartphones including games that measure learning mechanisms, activity bracelets), computational models, and real-world data may help to better identify patients with a high relapse risk and to offer targeted behavioral and pharmacotherapeutic interventions for vulnerable patients. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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14 pages, 403 KiB

Open AccessReview

The Potential of Cannabidiol as a Treatment for Psychosis and Addiction: Who Benefits Most? A Systematic Review

by Albert Batalla, Hella Janssen, Shiral S. Gangadin and Matthijs G. Bossong

J. Clin. Med. 2019, 8(7), 1058; https://doi.org/10.3390/jcm8071058 - 19 Jul 2019

Cited by 57 | Viewed by 16150

Abstract

The endogenous cannabinoid (eCB) system plays an important role in the pathophysiology of both psychotic disorders and substance use disorders (SUDs). The non-psychoactive cannabinoid compound, cannabidiol (CBD) is a highly promising tool in the treatment of both disorders. Here we review human clinical [...] Read more.

The endogenous cannabinoid (eCB) system plays an important role in the pathophysiology of both psychotic disorders and substance use disorders (SUDs). The non-psychoactive cannabinoid compound, cannabidiol (CBD) is a highly promising tool in the treatment of both disorders. Here we review human clinical studies that investigated the efficacy of CBD treatment for schizophrenia, substance use disorders, and their comorbidity. In particular, we examined possible profiles of patients who may benefit the most from CBD treatment. CBD, either as monotherapy or added to regular antipsychotic medication, improved symptoms in patients with schizophrenia, with particularly promising effects in the early stages of illness. A potential biomarker is the level of anandamide in blood. CBD and THC mixtures showed positive effects in reducing short-term withdrawal and craving in cannabis use disorders. Studies on schizophrenia and comorbid substance use are lacking. Future studies should focus on the effects of CBD on psychotic disorders in different stages of illness, together with the effects on comorbid substance use. These studies should use standardized measures to assess cannabis use. In addition, future efforts should be taken to study the relationship between the eCB system, GABA/glutamate, and the immune system to reveal the underlying neurobiology of the effects of CBD. Full article

(This article belongs to the Special Issue Assessment & Treatment of Addictions: New Tools for Old Problems)

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