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Claus BB, Scherbaum N, Specka M, Roser P, Bonnet U. Exploratory Growth Mixture Modeling of Cannabis-Withdrawal Syndrome Trajectories of Adult Pure Cannabis Dependents During Detoxification: Two Subtypes? J Psychoactive Drugs 2024; 56:551-562. [PMID: 37462539 DOI: 10.1080/02791072.2023.2229830] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 03/29/2023] [Accepted: 05/14/2023] [Indexed: 10/05/2024]
Abstract
As clinical studies about subtypes of the cannabis withdrawal syndrome (CWS) are scant, we performed a re-analysis of longitudinal data with German adult cannabis-users seeking inpatient cannabis detoxification-treatment. Sixty-seven cannabis-dependents without active comorbidity were included for growth-mixture-analysis (GMM) of their CWS-severity-trajectories during a scheduled 24-day detox-treatment. As of treatment-day 12, thirty-six (53.7%) of 67 patients were discharged after successful detoxification. This led to artificial imputations for I-GMM. Therefore, we preferred the results of the GMM including raw data-only (R-GMM). By both, I-GMM and R-GMM, we found two classes of CWS severity time-courses. Class one (n = 44, R-GMM) showed a continuously decreasing CWS-severity; class two (n = 23, R-GMM) exhibited a sharp peak (generally between days 2-6 post-cessation). A short inpatient treatment-period and low urinary 11-nor-9-carboxy-Δ9 -tetrahydrocannabinol-level upon admission predicted the peaking trajectory of R-GMM-class-two-CWS. Withdrawal syndrome medication (PRN), comorbidity, cannabis-history data and gender balance were not significantly different between the CWS-classes. Although possibly confounded by PRN-medication, this exploratory study supports the presence of two CWS-variants in adult cannabis-dependents, characterized by a slowly decreasing ("protracted") slope (class one) or a clear crescendo-decrescendo trajectory (class two). The latter was associated with a significantly shorter inpatient detoxification period and lower urinary THC-COOH-levels at admission.
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Affiliation(s)
- Benedikt Bernd Claus
- Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, EvangelIsches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University Duisburg-Essen, Castrop-Rauxel, Germany and Head of PedScience Research Institute. Datteln, Germany and Doctor rerum medicarum, University Duisburg-Essen; Essen, Germany
| | - Norbert Scherbaum
- Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen and Doctor rerum medicarum; University Duisburg-Essen, Essen, Germany
| | - Michael Specka
- Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen and Doctor rerum medicarum; University Duisburg-Essen, Essen, Germany
| | - Patrik Roser
- Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen and Doctor rerum medicarum; University Duisburg-Essen, Essen, Germany
| | - Udo Bonnet
- Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, EvangelIsches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University Duisburg-Essen, Castrop-Rauxel, Germany and Head of PedScience Research Institute. Datteln, Germany and Doctor rerum medicarum, University Duisburg-Essen; Essen, Germany
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Sherman BJ, Brasher ZE, Baker NL, McRae-Clark AL, Froeliger BE. Restructuring reward: A pilot study to enhance natural reward response in adults with cannabis use disorder. Drug Alcohol Depend 2023; 249:110830. [PMID: 37329729 PMCID: PMC10398752 DOI: 10.1016/j.drugalcdep.2023.110830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/31/2023] [Accepted: 06/08/2023] [Indexed: 06/19/2023]
Abstract
BACKGROUND Hedonic dysregulation is a core mechanism of addiction. There is a dearth of research on hedonic dysregulation in cannabis use disorder (CUD). The current study tested whether personalized scripted imagery may be an efficacious approach to remediate reward functioning in adults with CUD. METHODS Adults with CUD (n=10) and non-CUD controls (n=12) completed a single session personalized scripted imagery procedure. Non-drug (i.e. natural) reward and neutral scripts were transcribed and participants listened to the scripts in counterbalanced order. Primary outcomes included positive affect (PA), galvanic skin response (GSR), and cortisol and were assessed at four timepoints. Mixed effects models were used to compare between and within subject effects. RESULTS Mixed effects models revealed a Condition (reward vs. neutral) X Group (CUD vs. control) interaction (p=0.01) on PA response, indicating blunted PA response to the neutral script relative to the reward script in CUD participants. Likewise, GSR response in CUD participants was decreased in response to the neutral script relative to the reward script (p=0.034; interaction n.s.). An interaction effect of Group X PA on cortisol response was found (p=.036) indicating that cortisol was positively correlated with PA in healthy control participants, but not CUD participants. CONCLUSIONS Adults with CUD may demonstrate acute deficits in hedonic tone under neutral conditions relative to healthy controls. Personalized scripted imagery may be an efficacious tool to remediate hedonic dysregulation in CUD. Cortisol may play a role in healthy positive affect regulation warranting further investigation.
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Affiliation(s)
- Brian J Sherman
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, United States.
| | - Zoe E Brasher
- Department of Psychiatry, University of California, Los Angeles, United States
| | - Nathaniel L Baker
- Department of Public Health Sciences, Medical University of South Carolina, United States
| | - Aimee L McRae-Clark
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, United States; Department of Neuroscience, Medical University of South Carolina, United States; Ralph H. Johnson, VA Medical Center, Charleston, SC, United States
| | - Brett E Froeliger
- Departments of Psychiatry and Psychological Sciences, University of Missouri, United States
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Yeap ZJS, Marsault J, George TP, Mizrahi R, Rabin RA. Does tobacco dependence worsen cannabis withdrawal in people with and without schizophrenia-spectrum disorders? Am J Addict 2023; 32:367-375. [PMID: 36815595 DOI: 10.1111/ajad.13394] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 01/30/2023] [Accepted: 02/08/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Rates of cannabis use disorder (CUD) are higher in people with schizophrenia than in the general population. Irrespective of psychiatric diagnosis, tobacco co-use is prevalent in those with CUD and leads to poor cannabis cessation outcomes. The cannabis withdrawal syndrome is well-established and increases cannabis relapse risk. We investigated whether cannabis withdrawal severity differed as a function of high versus no/low tobacco dependence and psychiatric diagnosis in individuals with CUD. METHOD Men with CUD (N = 55) were parsed into four groups according to schizophrenia diagnosis and tobacco dependence severity using the Fagerstrom Test for Nicotine Dependence (FTND): men with schizophrenia with high tobacco dependence (SCT+, n = 13; FTND ≥ 5) and no/low tobacco dependence (SCT-, n = 22; FTND ≤ 4), and nonpsychiatric controls with high (CCT+, n = 7; FTND ≥ 5) and no/low (CCT-, n = 13; FTND ≤ 4) tobacco dependence. Participants completed the Marijuana Withdrawal Checklist following 12-h of cannabis abstinence. RESULTS There was a significant main effect of tobacco dependence on cannabis withdrawal severity (p < .001). Individuals with high tobacco dependence had significantly greater cannabis withdrawal severity (M = 13.85 [6.8]) compared to individuals with no/low tobacco dependence (M = 6.49, [4.9]). Psychiatric diagnosis and the interaction effects were not significant. Lastly, cannabis withdrawal severity positively correlated with FTND (r = .41, p = .002). CONCLUSION AND SCIENTIFIC SIGNIFICANCE Among individuals with CUD and high tobacco dependence, cannabis withdrawal severity was elevated twofold, irrespective of diagnosis, relative to individuals with CUD and no/low tobacco dependence. Findings from this study emphasize the importance of addressing tobacco co-use when treating CUD.
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Affiliation(s)
- Zac J S Yeap
- Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada
- Douglas Mental Health University Institute, Verdun, Quebec, Canada
| | - Justine Marsault
- Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada
- Douglas Mental Health University Institute, Verdun, Quebec, Canada
| | - Tony P George
- Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
- Centre for Complex Interventions and Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada
| | - Romina Mizrahi
- Douglas Mental Health University Institute, Verdun, Quebec, Canada
- Department of Psychiatry, McGill University, Montreal, Quebec, Canada
| | - Rachel A Rabin
- Douglas Mental Health University Institute, Verdun, Quebec, Canada
- Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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Sullivan RM, Wallace AL, Stinson EA, Montoto KV, Kaiver CM, Wade NE, Lisdahl KM. Assessment of Withdrawal, Mood, and Sleep Inventories After Monitored 3-Week Abstinence in Cannabis-Using Adolescents and Young Adults. Cannabis Cannabinoid Res 2022; 7:690-699. [PMID: 34678051 PMCID: PMC9587800 DOI: 10.1089/can.2021.0074] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Introduction: Among adolescents and young adults, cannabis use is prevalent. Prior studies characterizing withdrawal effects in this age range have primarily included treatment seeking or comorbid psychiatric samples; these studies have identified several affected domains, especially sleep, mood, and anxiety. The present study compared a community (i.e., nontreatment seeking) sample of cannabis-using and control participants on mood, anxiety, sleep, and withdrawal inventories during the course of a monitored 3-week cannabis abstinence period. Materials and Methods: Seventy-nine adolescent and young adult participants (cannabis-using group=37 and control group=42) were recruited from the community to undergo 3 weeks of confirmed abstinence (i.e., urine and sweat patch toxicology) and completion of Cannabis Withdrawal Symptom Criteria, State-Trait Anxiety Inventory, Beck's Depression Inventory, and Pittsburgh Sleep Quality Index across the study period. Repeated measures and cross-sectional regressions were used to examine main effects of group and interactions with time (where appropriate), while accounting for recent alcohol use and cotinine levels. Results: Cannabis-using participants reported higher mood (p=0.006), overall withdrawal (p=0.009), and sleep-related withdrawal (p<0.001) symptoms across abstinence compared to controls. Overall withdrawal severity (p=0.04) and sleep-related withdrawal symptoms (p=0.02) demonstrated a quadratic trajectory across the monitored abstinence periods, with an increase from baseline and subsequent decreases in symptom severity. No differences of anxiety scores (p=0.07) or trajectories (p=0.18) were observed. By study completion, groups did not differ among sleep quality components (all p's>.05). Conclusions: These findings revealed that nontreatment-seeking cannabis-using adolescents and young adults reported heightened total withdrawal symptoms during a 3-week sustained abstinence period relative to controls. Cannabis-using participants demonstrated an increase in withdrawal symptom trajectory during the first week followed by decreased symptoms from weeks 2 to 3, which contrasts with prior linear decreases observed in cannabis-using adolescent and young adults. More mood symptoms were observed in the cannabis-using group even while excluding for comorbid psychopathologies-along with significantly more sleep problems during the abstinence period. Implications include the necessity to provide psychoeducation for recreational, nontreatment-seeking cannabis-using individuals about cannabis withdrawal, mood symptoms, and sleep quality difficulties when cannabis cessation is attempted, to improve likelihood of long-term sustained abstinence.
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Affiliation(s)
- Ryan M. Sullivan
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA
| | - Alexander L. Wallace
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA
| | - Elizabeth A. Stinson
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA
| | - Karina V. Montoto
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA
| | - Christine M. Kaiver
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA
| | - Natasha E. Wade
- Department of Psychiatry, University of California, San Diego, San Diego, California, USA
| | - Krista M. Lisdahl
- Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA
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Razban M, Exadaktylos AK, Santa VD, Heymann EP. Cannabinoid hyperemesis syndrome and cannabis withdrawal syndrome: a review of the management of cannabis-related syndrome in the emergency department. Int J Emerg Med 2022; 15:45. [PMID: 36076180 PMCID: PMC9454163 DOI: 10.1186/s12245-022-00446-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Accepted: 08/19/2022] [Indexed: 11/17/2022] Open
Abstract
Background Cannabis-related medical consultations are increasing worldwide, a non-negligible public health issue; patients presenting to acute care traditionally complain of abdominal pain and vomiting. Often recurrent, these frequent consultations add to the congestion of already chronically saturated emergency department(s) (ED). In order to curb this phenomenon, a specific approach for these patients is key, to enable appropriate treatment and long-term follow-up. Objectives This study reviews cannabinoid hyperemesis syndrome (CHS) and cannabis withdrawal syndrome (CWS), in a bid to help promote better understanding and handling of pathologies associated with chronic cannabis use. Following a literature review, we present a novel therapeutic algorithm aimed at guiding clinicians, in a bid to improve long-term outcomes and prevent recurrences. Methods Using the keywords “Cannabis,” “Hyperemesis,” “Syndrome,” “Withdrawal,” and “Emergency Medicine,” we completed a literature review of three different electronic databases (PubMed®, Google scholar®, and Cochrane®), up to November 2021. Results Although often presenting with similar symptoms such as abdominal pain and vomiting, cannabinoid hyperemesis syndrome (CHS) and cannabis withdrawal syndrome (CWS) are the result of two differing pathophysiological processes. Distinguishing between these two syndromes is essential to provide appropriate symptomatic options. Conclusion The correct identification of the underlying cannabis-related syndrome, and subsequent therapeutic choice, may help decrease ED presentations. Our study emphasizes the importance of both acute care and long-term outpatient follow-up, as key processes in cannabis-related disorder treatment.
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Affiliation(s)
- Mohammad Razban
- Department of Internal Medicine, University Hospital of Geneva, Geneva, Switzerland. .,University of Bern, Bern, Switzerland.
| | | | - Vincent Della Santa
- Department of Emergency Medicine, Cantonal Hospital of Neuchatel, Neuchatel, Switzerland
| | - Eric P Heymann
- Department of Emergency Medicine, Cantonal Hospital of Neuchatel, Neuchatel, Switzerland
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Factors Associated With Past-year and Lifetime Prevalence of Cannabis Withdrawal: A Secondary Analysis. CANADIAN JOURNAL OF ADDICTION 2022. [DOI: 10.1097/cxa.0000000000000155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
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Connor JP, Stjepanović D, Budney AJ, Le Foll B, Hall WD. Clinical management of cannabis withdrawal. Addiction 2022; 117:2075-2095. [PMID: 34791767 PMCID: PMC9110555 DOI: 10.1111/add.15743] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 10/27/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND AND AIMS Cannabis withdrawal is a well-characterized phenomenon that occurs in approximately half of regular and dependent cannabis users after abrupt cessation or significant reductions in cannabis products that contain Δ9 -tetrahydrocannabinol (THC). This review describes the diagnosis, prevalence, course and management of cannabis withdrawal and highlights opportunities for future clinical research. METHODS Narrative review of literature. RESULTS Symptom onset typically occurs 24-48 hours after cessation and most symptoms generally peak at days 2-6, with some symptoms lasting up to 3 weeks or more in heavy cannabis users. The most common features of cannabis withdrawal are anxiety, irritability, anger or aggression, disturbed sleep/dreaming, depressed mood and loss of appetite. Less common physical symptoms include chills, headaches, physical tension, sweating and stomach pain. Despite limited empirical evidence, supportive counselling and psychoeducation are the first-line approaches in the management of cannabis withdrawal. There are no medications currently approved specifically for medically assisted withdrawal (MAW). Medications have been used to manage short-term symptoms (e.g. anxiety, sleep, nausea). A number of promising pharmacological agents have been examined in controlled trials, but these have been underpowered and positive findings not reliably replicated. Some (e.g. cannabis agonists) are used 'off-label' in clinical practice. Inpatient admission for MAW may be clinically indicated for patients who have significant comorbid mental health disorders and polysubstance use to avoid severe complications. CONCLUSIONS The clinical significance of cannabis withdrawal is that its symptoms may precipitate relapse to cannabis use. Complicated withdrawal may occur in people with concurrent mental health and polysubstance use.
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Affiliation(s)
- Jason P. Connor
- National Centre for Youth Substance Use ResearchThe University of QueenslandSt LuciaQLDAustralia,Discipline of Psychiatry, Faculty of MedicineThe University of QueenslandHerstonQLDAustralia
| | - Daniel Stjepanović
- National Centre for Youth Substance Use ResearchThe University of QueenslandSt LuciaQLDAustralia
| | - Alan J. Budney
- Center for Technology and Behavioral HealthGeisel School of Medicine at DartmouthLebanonNHUSA
| | - Bernard Le Foll
- Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental HealthUniversity of TorontoONCanada,Departments of Family and Community Medicine, Psychiatry, Pharmacology and ToxicologyUniversity of TorontoONCanada
| | - Wayne D. Hall
- National Centre for Youth Substance Use ResearchThe University of QueenslandSt LuciaQLDAustralia,Queensland Alliance for Environmental Health SciencesThe University of QueenslandWoolloongabbaQLDAustralia
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Girasek H, Nagy VA, Fekete S, Ungvari GS, Gazdag G. Prevalence and correlates of aggressive behavior in psychiatric inpatient populations. World J Psychiatry 2022; 12:1-23. [PMID: 35111577 PMCID: PMC8783168 DOI: 10.5498/wjp.v12.i1.1] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/18/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Aggressive behavior in patients with psychiatric disorders is attracting increasing research interest. One reason for this is that psychiatric patients are generally considered more likely to be aggressive, which raises a related question of whether diagnoses of psychiatric disorders predict the prevalence of aggressive behavior. Predicting aggression in psychiatric wards is crucial, because aggressive behavior not only endangers the safety of both patients and staff, but it also extends the hospitalization times. Predictions of aggressive behavior also need careful attention to ensure effective treatment planning. This literature review explores the relationship between aggressive behavior and psychiatric disorders and syndromes (dementia, psychoactive substance use, acute psychotic disorder, schizophrenia, bipolar affective disorder, major depressive disorder, obsessive-compulsive disorder, personality disorders and intellectual disability). The prevalence of aggressive behavior and its underlying risk factors, such as sex, age, comorbid psychiatric disorders, socioeconomic status, and history of aggressive behavior are discussed as these are the components that mostly contribute to the increased risk of aggressive behavior. Measurement tools commonly used to predict and detect aggressive behavior and to differentiate between different forms of aggressive behavior in both research and clinical practice are also reviewed. Successful aggression prevention programs can be developed based on the current findings of the correlates of aggressive behavior in psychiatric patients.
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Affiliation(s)
- Hunor Girasek
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
| | - Vanda Adél Nagy
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
| | - Szabolcs Fekete
- Department of Psychiatry, National Institute of Forensic Psychiatry, Budapest 1108, Hungary
- School of PhD Studies, Semmelweis University, Budapest 1085, Hungary
| | - Gabor S Ungvari
- Division of Psychiatry, School of Medicine, University of Western Australia, Crawley 6009, Australia
- Section of Psychiatry, University of Notre Dame, Fremantle 6160, Australia
| | - Gábor Gazdag
- Department of Psychiatry and Psychiatric Rehabilitation, Jahn Ferenc South Pest Hospital, Budapest 1204, Hungary
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, Budapest 1083, Hungary
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Coughlin LN, Ilgen MA, Jannausch M, Walton MA, Bohnert KM. Progression of cannabis withdrawal symptoms in people using medical cannabis for chronic pain. Addiction 2021; 116:2067-2075. [PMID: 33400332 PMCID: PMC8363170 DOI: 10.1111/add.15370] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 08/26/2020] [Accepted: 11/30/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND AND AIMS Research from cohorts of individuals with recreational cannabis use indicates that cannabis withdrawal symptoms are reported by more than 40% of those using regularly. Withdrawal symptoms are not well understood in those who use cannabis for medical purposes. Therefore, we prospectively examined the stability of withdrawal symptoms in individuals using cannabis to manage chronic pain. DESIGN, SETTING, PARTICIPANTS Using latent class analysis (LCA) we examined baseline cannabis withdrawal to derive symptom profiles. Then, using latent transition analysis (LTA) we examined the longitudinal course of withdrawal symptoms across the time points. Exploratory analyses examined demographic and clinical characteristics predictive of withdrawal class and transitioning to more or fewer withdrawal symptoms over time. A cohort of 527 adults with chronic pain seeking medical cannabis certification or re-certification was recruited between February 2014 and June 2015. Participants were recruited from medical cannabis clinic waiting rooms in Michigan, USA. Participants were predominantly white (82%) and 49% identified as male, with an average age of 45.6 years (standard deviation = 12.8). MEASUREMENTS Baseline, 12-month and 24-month assessments of withdrawal symptoms using the Marijuana Withdrawal Checklist-revised. FINDINGS A three-class LCA model including a mild (41%), moderate (34%) and severe (25%) symptom class parsimoniously represented withdrawal symptoms experienced by people using medical cannabis. Stability of withdrawal symptoms using a three-class LTA at 12 and 24 months ranged from 0.58 to 0.87, with the most stability in the mild withdrawal class. Younger age predicted greater severity and worsening of withdrawal over time. CONCLUSIONS Adults with chronic pain seeking medical cannabis certification or re-certification appear to experience mild to severe withdrawal symptoms. Withdrawal symptoms tend to be stable over a 2-year period, but younger age is predictive of worse symptoms and of an escalating withdrawal trajectory.
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Affiliation(s)
- Lara N. Coughlin
- Addiction Center, Department of Psychiatry, University of Michigan
| | - Mark A. Ilgen
- Addiction Center, Department of Psychiatry, University of Michigan,VA Center for Clinical Management Research, VA Ann Arbor Healthcare System
| | - Mary Jannausch
- Addiction Center, Department of Psychiatry, University of Michigan,VA Center for Clinical Management Research, VA Ann Arbor Healthcare System
| | - Maureen A. Walton
- Addiction Center, Department of Psychiatry, University of Michigan,Injury Prevention Center, University of Michigan
| | - Kipling M. Bohnert
- Addiction Center, Department of Psychiatry, University of Michigan,VA Center for Clinical Management Research, VA Ann Arbor Healthcare System,Department of Epidemiology and Biostatistics, Michigan State University
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Kesner AJ, Lovinger DM. Cannabis use, abuse, and withdrawal: Cannabinergic mechanisms, clinical, and preclinical findings. J Neurochem 2021; 157:1674-1696. [PMID: 33891706 PMCID: PMC9291571 DOI: 10.1111/jnc.15369] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 04/12/2021] [Accepted: 04/12/2021] [Indexed: 12/14/2022]
Abstract
Cannabis sativa is the most widely used illicit drug in the world. Its main psychoactive component is delta-9-tetrahydrocannabinol (THC), one of over 100 phytocannabinoid compounds produced by the cannabis plant. THC is the primary compound that drives cannabis abuse potential and is also used and prescribed medically for therapeutic qualities. Despite its therapeutic potential, a significant subpopulation of frequent cannabis or THC users will develop a drug use syndrome termed cannabis use disorder. Individuals suffering from cannabis use disorder exhibit many of the hallmarks of classical addictions including cravings, tolerance, and withdrawal symptoms. Currently, there are no efficacious treatments for cannabis use disorder or withdrawal symptoms. This makes both clinical and preclinical research on the neurobiological mechanisms of these syndromes ever more pertinent. Indeed, basic research using animal models has provided valuable evidence of the neural molecular and cellular actions of cannabis that mediate its behavioral effects. One of the main components being central action on the cannabinoid type-one receptor and downstream intracellular signaling related to the endogenous cannabinoid system. Back-translational studies have provided insight linking preclinical basic and behavioral biology research to better understand symptoms observed at the clinical level. This narrative review aims to summarize major research elucidating the molecular, cellular, and behavioral manifestations of cannabis/THC use that play a role in cannabis use disorder and withdrawal.
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Affiliation(s)
- Andrew J. Kesner
- Laboratory for Integrative NeuroscienceNational Institute on Alcohol Abuse and AlcoholismCenter on Compulsive BehaviorsNational Institutes of HealthBethesdaMDUSA
| | - David M. Lovinger
- Laboratory for Integrative NeuroscienceNational Institute on Alcohol Abuse and AlcoholismCenter on Compulsive BehaviorsNational Institutes of HealthBethesdaMDUSA
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Steele JL, Peralta RL. Are Polydrug Users More Physically and Verbally Aggressive? An Assessment of Aggression Among Mono- Versus Polydrug Users in a University Sample. JOURNAL OF INTERPERSONAL VIOLENCE 2020; 35:4444-4467. [PMID: 29294803 DOI: 10.1177/0886260517715024] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Early research has revealed that patterns of aggression and antisocial behavior are present among polydrug users. Often missing from this discourse is the examination of whether polydrug users are quantitatively different from monodrug users in their use of aggression. Theoretical perspectives are often centered on the psychopharmacological effects of substance use on behavior. Consideration of possible poly- versus monodrug use differences and their impact on aggression has not been investigated. Data from this study were derived from a sample of Midwestern university students (N = 793). The relationship between violence, aggression, and concurrent polydrug use in the last year is assessed with a series of multivariate ordinary least squares (OLS) regression models. Results demonstrate that higher incidents of physical and verbal aggression are reported among polydrug users compared to monodrug users and abstainers. When analyses were broken down by polydrug users (those who engaged in alcohol/marijuana and alcohol/NMUPD [nonmedical use of prescription drugs] stimulants), polydrug users reported higher levels of physical aggression compared to monodrug users. Similarly, monodrug users reported higher levels of physical aggression compared to nonusers. This research extends our understanding of aggression among users from two different subcategories: polydrug users in comparison to those who only engage in one form of substance use. Scholars and practitioners who work with violent offenders should consider patterns of drug use behavior when addressing substance use-related aggression.
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Bahji A, Stephenson C, Tyo R, Hawken ER, Seitz DP. Prevalence of Cannabis Withdrawal Symptoms Among People With Regular or Dependent Use of Cannabinoids: A Systematic Review and Meta-analysis. JAMA Netw Open 2020; 3:e202370. [PMID: 32271390 PMCID: PMC7146100 DOI: 10.1001/jamanetworkopen.2020.2370] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
IMPORTANCE Cannabis withdrawal syndrome (CWS)-a diagnostic indicator of cannabis use disorder-commonly occurs on cessation of heavy and prolonged cannabis use. To date, the prevalence of CWS syndrome has not been well described, nor have the factors potentially associated with CWS. OBJECTIVES To estimate the prevalence of CWS among individuals with regular or dependent use of cannabinoids and identify factors associated with CWS. DATA SOURCES A search of literature from database inception to June 19, 2019, was performed using MEDLINE, Embase, PsycINFO, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, ProQuest, Allied and Complementary Medicine, and Psychiatry online, supplemented by manual searches of reference lists of included articles. STUDY SELECTION Articles were included if they (1) were published in English, (2) reported on individuals with regular use of cannabinoids or cannabis use disorder as a primary study group, (3) reported on the prevalence of CWS or CWS symptoms using a validated instrument, (4) reported the prevalence of CWS, and (5) used an observational study design (eg, cohort or cross-sectional). DATA EXTRACTION AND SYNTHESIS All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. Cannabis withdrawal syndrome prevalence was estimated using a random-effects meta-analysis model, alongside stratification and meta-regression to characterize heterogeneity. MAIN OUTCOMES AND MEASURES Cannabis withdrawal syndrome prevalence was reported as a percentage with 95% CIs. RESULTS Of 3848 unique abstracts, 86 were selected for full-text review, and 47 studies, representing 23 518 participants, met all inclusion criteria. Of 23 518 participants included in the analysis, 16 839 were white (72%) and 14 387 were men (69%); median (SD) age was 29.9 (9.0) years. The overall pooled prevalence of CWS was 47% (6469 of 23 518) (95% CI, 41%-52%), with significant heterogeneity between estimates (I2 = 99.2%). When stratified by source, the prevalence of CWS was 17% (95% CI, 13%-21%) in population-based samples, 54% in outpatient samples (95% CI, 48%-59%), and 87% in inpatient samples (95% CI, 79%-94%), which were significantly different (P < .001). Concurrent cannabis (β = 0.005, P < .001), tobacco (β = 0.002, P = .02), and other substance use disorders (β = 0.003, P = .05) were associated with a higher CWS prevalence, as was daily cannabis use (β = 0.004, P < .001). CONCLUSIONS AND RELEVANCE These findings suggest that cannabis withdrawal syndrome appears to be prevalent among regular users of cannabis. Clinicians should be aware of the prevalence of CWS in order to counsel patients and support individuals who are reducing their use of cannabis.
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Affiliation(s)
- Anees Bahji
- Department of Public Health Sciences, Queen’s University, Kingston, Ontario, Canada
- Department of Psychiatry, Queen’s University, Kingston, Ontario, Canada
| | - Callum Stephenson
- Queen’s University School of Kinesiology and Health Studies, Kingston, Ontario, Canada
| | - Richard Tyo
- Department of Psychiatry, Queen’s University, Kingston, Ontario, Canada
| | - Emily R. Hawken
- Department of Psychiatry, Queen’s University, Kingston, Ontario, Canada
| | - Dallas P. Seitz
- Department of Public Health Sciences, Queen’s University, Kingston, Ontario, Canada
- Department of Psychiatry, Queen’s University, Kingston, Ontario, Canada
- Cumming School of Medicine, Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
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Van Kampen AD, Cousijn J, Engel C, Rinck M, Dijkstra BAG. Attentional bias, craving and cannabis use in an inpatient sample of adolescents and young adults diagnosed with cannabis use disorder: The moderating role of cognitive control. Addict Behav 2020; 100:106126. [PMID: 31605838 DOI: 10.1016/j.addbeh.2019.106126] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 09/04/2019] [Accepted: 09/09/2019] [Indexed: 11/18/2022]
Abstract
Motivational processes like attentional bias and craving have been related to substance use. However, results are inconclusive. The present cross-sectional study was designed to replicate and extend previous research by investigating the relationships between attentional bias, craving, cognitive control and (severity of) cannabis use in a sample of inpatient adolescents and young adults (aged 18-30) diagnosed with CUD according to DSM-5. Contrary to expectations, our sample did not show attentional bias for cannabis words, neither did attentional bias correlate with craving, cognitive control or (severity of) cannabis use. In line with our hypotheses, however, increased session-induced craving was correlated to more daily cannabis use and reduced cognitive control. Furthermore, participants who displayed reduced cognitive control used more cannabis per day. A bootstrapped hierarchical regression model showed that, contrary to expectations, cognitive control did not modulate the relationships between attentional bias, craving and cannabis use. This study highlights the unique role of craving in relation to cannabis use and extends previous findings that cognitive control appears to have no moderating role regarding cannabis use disorder. Based on our results, it might well be that the underlying mechanisms of cannabis use disorder differ from those in other substance use disorders.
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Affiliation(s)
| | - J Cousijn
- ADAPT-Research Center, Department of Psychology, University of Amsterdam, the Netherlands
| | - C Engel
- Iriszorg, Nijmegen, the Netherlands
| | - M Rinck
- Radboud University, Behavioural Science Institute, Nijmegen, the Netherlands
| | - B A G Dijkstra
- Radboud University, Behavioural Science Institute, Nijmegen, the Netherlands; Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), Nijmegen, the Netherlands; Novadic-Kentron, Vugt, the Netherlands
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14
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Aguinaldo LD, Squeglia LM, Gray KM, Coronado C, Lees B, Tomko RL, Jacobus J. Behavioral Treatments for Adolescent Cannabis Use Disorder: a Rationale for Cognitive Retraining. CURRENT ADDICTION REPORTS 2019; 6:437-442. [PMID: 32257767 DOI: 10.1007/s40429-019-00287-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Purpose of Review Adolescent cannabis use represents a significant public health concern. Cannabis experimentation typically begins in adolescence and increases the odds of meeting criteria for cannabis use disorder. Cannabis use disorder is associated with numerous short- and long-term adverse consequences for adolescents, highlighting the critical need for efficacious behavioral treatments. This brief review aims to synthesize the state of the behavioral treatment literature on adolescents with cannabis use disorder and to discuss new pathways to leverage neuroscience to inform novel targets for behavioral intervention. Recent Findings To date, effective treatment options for adolescent cannabis use disorder that have been tested in randomized controlled trials include cognitive behavioral therapy, motivational enhancement therapy, and multidimensional family therapy. However, established behavioral treatment approaches focus on higher-order cognitive control and have only been modestly effective. Summary There is a need to develop new pathways that translate neuroscience findings into novel targets for behavioral interventions.
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Affiliation(s)
- Laika D Aguinaldo
- Department of Psychiatry, University of California, 9500 Gilman Drive (0862) La Jolla, San Diego, CA 92093-0862, USA
| | - Lindsay M Squeglia
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA
| | - Kevin M Gray
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA
| | - Clarisa Coronado
- Department of Psychiatry, University of California, 9500 Gilman Drive (0862) La Jolla, San Diego, CA 92093-0862, USA
| | - Briana Lees
- The Matilda Centre for Research in Mental Health and Substance Use, University of Sydney, Sydney, NSW, Australia
| | - Rachel L Tomko
- Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA
| | - Joanna Jacobus
- Department of Psychiatry, University of California, 9500 Gilman Drive (0862) La Jolla, San Diego, CA 92093-0862, USA
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15
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Livne O, Shmulewitz D, Lev-Ran S, Hasin DS. DSM-5 cannabis withdrawal syndrome: Demographic and clinical correlates in U.S. adults. Drug Alcohol Depend 2019; 195:170-177. [PMID: 30361043 PMCID: PMC6359953 DOI: 10.1016/j.drugalcdep.2018.09.005] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/05/2018] [Accepted: 09/06/2018] [Indexed: 01/24/2023]
Abstract
BACKGROUND Cannabis withdrawal syndrome (CWS) was newly added to the Diagnostic and Statistical Manual of Mental Disorders in its most recent edition, DSM-5. With cannabis use increasing among U.S. adults, information is needed about the prevalence and correlates of DSM-5 CWS in the general population. This study presents nationally representative findings on the prevalence, sociodemographic and clinical correlates of DSM-5 CWS among U.S. adults. METHOD Participants ≥18 years were interviewed in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) in 2012-2013. Among the sub-sample of frequent cannabis users in the prior 12 months (≥3 times a week; N = 1527), the prevalence and demographic and clinical correlates of DSM-5 CWS were examined. RESULTS In frequent cannabis users, the prevalence of CWS was 12.1%. The most common withdrawal symptoms among those with CWS were nervousness/anxiety (76.3%), hostility (71.9%), sleep difficulty (68.2%) and depressed mood (58.9%). CWS was associated with significant disability (p < 0.001), and with mood disorders (adjusted odds ratios [aOR] = 1.9-2.6), anxiety disorders (aOR = 2.4-2.5), personality disorders (aOR = 1.7-2.2) and family history of depression (aOR = 2.5) but not personal history of other substance use disorders or family history of substance use problems. CONCLUSIONS CWS is highly comorbid and disabling. Its shared symptoms with depressive and anxiety disorders call for clinician awareness of CWS and the factors associated with it to promote more effective treatment among frequent cannabis users.
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Affiliation(s)
- Ofir Livne
- Lev Hasharon Medical Center, P.O. Box 90000, Netanya 42100, Israel
| | - Dvora Shmulewitz
- New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA,Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA
| | - Shaul Lev-Ran
- Lev Hasharon Medical Center, P.O. Box 90000, Netanya 42100, Israel,Sackler Faculty of Medicine, Tel Aviv University, P.O. Box 39040, Ramat Aviv, Tel Aviv 69978, Israel
| | - Deborah S. Hasin
- New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA,Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA,Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th Street, New York, NY 10032, USA
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16
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Abstract
BACKGROUND Globally, cannabis use is prevalent and widespread. There are currently no pharmacotherapies approved for treatment of cannabis use disorders.This is an update of a Cochrane Review first published in the Cochrane Library in Issue 12, 2014. OBJECTIVES To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or no pharmacotherapy (supportive care) for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. SEARCH METHODS We updated our searches of the following databases to March 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and Web of Science. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs involving the use of medications to treat cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in people diagnosed as cannabis dependent or who were likely to be dependent. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. MAIN RESULTS We included 21 RCTs involving 1755 participants: 18 studies recruited adults (mean age 22 to 41 years); three studies targeted young people (mean age 20 years). Most (75%) participants were male. The studies were at low risk of performance, detection and selective outcome reporting bias. One study was at risk of selection bias, and three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications were diverse, as were the outcomes reported, which limited the extent of analysis.Abstinence at end of treatment was no more likely with Δ9-tetrahydrocannabinol (THC) preparations than with placebo (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.64 to 1.52; 305 participants; 3 studies; moderate-quality evidence). For selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine, there was no difference in the likelihood of abstinence at end of treatment compared to placebo (low- to very low-quality evidence).There was qualitative evidence of reduced intensity of withdrawal symptoms with THC preparations compared to placebo. For other pharmacotherapies, this outcome was either not examined, or no significant differences was reported.Adverse effects were no more likely with THC preparations (RR 1.02, 95% CI 0.89 to 1.17; 318 participants; 3 studies) or N-acetylcysteine (RR 0.94, 95% CI 0.71 to 1.23; 418 participants; 2 studies) compared to placebo (moderate-quality evidence). For SSRI antidepressants, mixed action antidepressants, buspirone and N-acetylcysteine, there was no difference in adverse effects compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of withdrawal from treatment due to adverse effects with THC preparations, SSRIs antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, buspirone and N-acetylcysteine compared to placebo (low- to very low-quality evidence).There was no difference in the likelihood of treatment completion with THC preparations, SSRI antidepressants, mixed action antidepressants and buspirone compared to placebo (low- to very low-quality evidence) or with N-acetylcysteine compared to placebo (RR 1.06, 95% CI 0.93 to 1.21; 418 participants; 2 studies; moderate-quality evidence). Anticonvulsants and mood stabilisers appeared to reduce the likelihood of treatment completion (RR 0.66, 95% CI 0.47 to 0.92; 141 participants; 3 studies; low-quality evidence).Available evidence on gabapentin (anticonvulsant), oxytocin (neuropeptide) and atomoxetine was insufficient for estimates of effectiveness. AUTHORS' CONCLUSIONS There is incomplete evidence for all of the pharmacotherapies investigated, and for many outcomes the quality of the evidence was low or very low. Findings indicate that SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine are probably of little value in the treatment of cannabis dependence. Given the limited evidence of efficacy, THC preparations should be considered still experimental, with some positive effects on withdrawal symptoms and craving. The evidence base for the anticonvulsant gabapentin, oxytocin, and N-acetylcysteine is weak, but these medications are also worth further investigation.
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Affiliation(s)
- Suzanne Nielsen
- Monash UniversityMonash Addiction Research CentrePeninsula CampusMcMahons RoadFrankstonVICAustralia3199
| | - Linda Gowing
- University of AdelaideDiscipline of PharmacologyFrome RoadAdelaideSouth AustraliaAustralia5005
| | - Pamela Sabioni
- Centre for Addiction and Mental Health; University of TorontoTranslational Addiction Research Laboratory33 Russell StreetTorontoONCanada
| | - Bernard Le Foll
- Centre for Addiction and Mental Health; University of TorontoTranslational Addiction Research Laboratory33 Russell StreetTorontoONCanada
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Cousijn J, van Duijvenvoorde ACK. Cognitive and Mental Health Predictors of Withdrawal Severity During an Active Attempt to Cut Down Cannabis Use. Front Psychiatry 2018; 9:301. [PMID: 30050473 PMCID: PMC6050370 DOI: 10.3389/fpsyt.2018.00301] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 06/18/2018] [Indexed: 01/30/2023] Open
Abstract
A milestone in cannabis research is the establishment of a clinically relevant cannabis withdrawal syndrome, yet little is known about the underlying mechanisms. We investigated the predictive role of mental health and cognitive factors in withdrawal severity during an active attempt to cut down, relative to uninterrupted cannabis use. Ninety heavy cannabis users were randomly assigned to an experimental or control group. The experimental group was asked to cut down substance use for 1 week. Past week substance use, substance use-related problems, depressive symptoms, cravings, and cognitive control were assessed at baseline. Past week substance use and withdrawal severity were assessed at follow-up. The experimental group reduced their cannabis use more and experienced more withdrawal than the control group. Hierarchical regression analysis per predictor indicated that cannabis use-related problems, depressive symptoms, and cannabis craving, but not cognitive control, predicted stronger withdrawal. Craving uniquely predicted withdrawal in the experimental group. A combined hierarchical regression indicated that only depressive symptoms and cannabis use-related problems uniquely predicted withdrawal across groups. These results suggest that depressive symptoms and cannabis use-related problems are generally indicative of cannabis withdrawal severity, whereas craving specifically predicts cannabis withdrawal during an active attempt to cut-down cannabis use.
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Affiliation(s)
- Janna Cousijn
- Addiction Development and Psychopathology Lab, Department of Psychology, University of Amsterdam, Amsterdam, Netherlands
| | - A C K van Duijvenvoorde
- Brain and Development Lab, Department of Psychology, Leiden University, Leiden, Netherlands.,Leiden Institute for Brain and Cognition, Leiden, Netherlands
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18
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Hasin DS. US Epidemiology of Cannabis Use and Associated Problems. Neuropsychopharmacology 2018; 43:195-212. [PMID: 28853439 PMCID: PMC5719106 DOI: 10.1038/npp.2017.198] [Citation(s) in RCA: 395] [Impact Index Per Article: 56.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 08/17/2017] [Accepted: 08/18/2017] [Indexed: 12/12/2022]
Abstract
This review provides an overview of the changing US epidemiology of cannabis use and associated problems. Adults and adolescents increasingly view cannabis as harmless, and some can use cannabis without harm. However, potential problems include harms from prenatal exposure and unintentional childhood exposure; decline in educational or occupational functioning after early adolescent use, and in adulthood, impaired driving and vehicle crashes; cannabis use disorders (CUD), cannabis withdrawal, and psychiatric comorbidity. Evidence suggests national increases in cannabis potency, prenatal and unintentional childhood exposure; and in adults, increased use, CUD, cannabis-related emergency room visits, and fatal vehicle crashes. Twenty-nine states have medical marijuana laws (MMLs) and of these, 8 have recreational marijuana laws (RMLs). Many studies indicate that MMLs or their specific provisions did not increase adolescent cannabis use. However, the more limited literature suggests that MMLs have led to increased cannabis potency, unintentional childhood exposures, adult cannabis use, and adult CUD. Ecological-level studies suggest that MMLs have led to substitution of cannabis for opioids, and also possibly for psychiatric medications. Much remains to be determined about cannabis trends and the role of MMLs and RMLs in these trends. The public, health professionals, and policy makers would benefit from education about the risks of cannabis use, the increases in such risks, and the role of marijuana laws in these increases.
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Affiliation(s)
- Deborah S Hasin
- Columbia University and New York State Psychiatric Institute, New York, NY, USA
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19
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Schuster RM, Fontaine M, Nip E, Zhang H, Hanly A, Evins AE. Prolonged cannabis withdrawal in young adults with lifetime psychiatric illness. Prev Med 2017; 104:40-45. [PMID: 28242263 PMCID: PMC5572754 DOI: 10.1016/j.ypmed.2017.02.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 02/17/2017] [Accepted: 02/18/2017] [Indexed: 01/22/2023]
Abstract
Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18-25, recruited from the Boston-area in 2015-2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD+ vs PD-), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD+ and PD- groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46)=3.8, p=0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD- had significantly reduced withdrawal symptom severity in abstinent week one [t(46)=-2.2, p=0.03], while PD+ did not report improved withdrawal symptoms until the second abstinent week [t(46)=-4.1, p=0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting.
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Affiliation(s)
- Randi Melissa Schuster
- Center for Addiction Medicine, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
| | - Madeleine Fontaine
- Center for Addiction Medicine, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Emily Nip
- Center for Addiction Medicine, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Haiyue Zhang
- Department of Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Ailish Hanly
- Center for Addiction Medicine, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; University of Massachusetts Medical School, Worcester, MA, USA
| | - A Eden Evins
- Center for Addiction Medicine, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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20
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Meier MH. Associations between butane hash oil use and cannabis-related problems. Drug Alcohol Depend 2017; 179:25-31. [PMID: 28750253 DOI: 10.1016/j.drugalcdep.2017.06.015] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 06/11/2017] [Accepted: 06/12/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND High-potency cannabis concentrates are increasingly popular in the United States, and there is concern that use of high-potency cannabis might increase risk for cannabis-related problems. However, little is known about the potential negative consequences of concentrate use. This study reports on associations between past-year use of a high-potency cannabis concentrate, known as butane hash oil (BHO), and cannabis-related problems. METHODS A sample of 821 college students were recruited to complete a survey about their health and behavior. Participants who had used cannabis in the past year (33%, n=273) completed questions about their cannabis use, including their use of BHO and cannabis-related problems in eight domains: physical dependence, impaired control, academic-occupational problems, social-interpersonal problems, self-care problems, self-perception, risk behavior, and blackouts. RESULTS Approximately 44% (n=121) of past-year cannabis users had used BHO in the past year. More frequent BHO use was associated with higher levels of physical dependence (RR=1.8, p<0.001), impaired control (RR=1.3, p<0.001), cannabis-related academic/occupational problems (RR=1.5, p=0.004), poor self-care (RR=1.3, p=0.002), and cannabis-related risk behavior (RR=1.2, p=0.001). After accounting for sociodemographic factors, age of onset of cannabis use, sensation seeking, overall frequency of cannabis use, and frequency of other substance use, BHO use was still associated with higher levels of physical dependence (RR=1.2, p=0.014). CONCLUSIONS BHO use is associated with greater physiological dependence on cannabis, even after accounting for potential confounders. Longitudinal research is needed to determine if cannabis users with higher levels of physiological dependence seek out BHO and/or if BHO use increases risk for physiological dependence.
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Affiliation(s)
- Madeline H Meier
- Department of Psychology, Arizona State University, PO Box 871104, Tempe, AZ 85287-1104, United States.
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Buckner JD, Walukevich KA, Zvolensky MJ, Gallagher MW. Emotion regulation and coping motives serially affect cannabis cessation problems among dually diagnosed outpatients. PSYCHOLOGY OF ADDICTIVE BEHAVIORS 2017; 31:839-845. [PMID: 28846000 DOI: 10.1037/adb0000310] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Little empirical work has evaluated why anxious cannabis users are especially vulnerable to poorer cannabis cessation outcomes. Presumably, these individuals rely on cannabis because they have difficulties with emotion regulation and they therefore use cannabis to manage their negative emotions. The current study examined the direct and indirect effects of anxiety severity on a range of cannabis cessation variables among 79 (63.3% non-Hispanic White; 43.0% female) adults with anxiety disorders seeking outpatient treatment for cannabis use disorder. The independent and serial indirect effects of difficulties with emotion regulation and coping motives were examined in relation to the anxiety-cannabis variables. Anxiety severity was directly and robustly related to greater cannabis withdrawal symptom severity, less self-efficacy to refrain from using cannabis in emotionally distressing situations, and more reasons for quitting. Anxiety was indirectly related to cannabis outcomes via the serial effects of emotion regulation and coping motives. These findings document the important role of emotion regulation and coping motives in the relations of anxiety with cannabis cessation variables among dually diagnosed outpatients. (PsycINFO Database Record
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Pokorski I, Clement N, Phung N, Weltman M, Fu S, Copeland J. Cannabidiol in the management of in-patient cannabis withdrawal: clinical case series. FUTURE NEUROLOGY 2017. [DOI: 10.2217/fnl-2016-0035] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: To assess the feasibility of the use of cannabidiol (CBD) for the management of cannabis withdrawal. Patients & methods: Eight participants were admitted to an in-patient detoxification facility for a 7-day open-label trial of CBD. Five participants received 600 mg of CBD and three participants received 1200 mg of CBD. Participants returned for a 28-day follow-up interview. Results & conclusion: CBD was well tolerated by all participants. Five completed the full treatment period and abstinence was maintained by four participants at day 28 follow-up. All those receiving the higher dose completed treatment and achieved abstinence at follow-up. This pilot study suggests that further exploration of CBD as a pharmacological adjunctive therapy for cannabis withdrawal and dependence is warranted. Registration ACTRN1261400024866.
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Affiliation(s)
- Izabella Pokorski
- National Cannabis Prevention & Information Centre, University of New South Wales, Medicine, Sydney, New South Wales 2052, Australia
| | - Nicole Clement
- National Cannabis Prevention & Information Centre, University of New South Wales, Medicine, Sydney, New South Wales 2052, Australia
| | - Nghi Phung
- Western Sydney Local Health District, New South Wales Health Department, New South Wales 5041, Australia
| | - Marin Weltman
- Western Sydney Local Health District, New South Wales Health Department, New South Wales 5041, Australia
| | - Shanlin Fu
- University of Technology, Sydney 2007, Australia
| | - Jan Copeland
- National Cannabis Prevention & Information Centre, University of New South Wales, Medicine, Sydney, New South Wales 2052, Australia
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Schlienz NJ, Budney AJ, Lee DC, Vandrey R. Cannabis Withdrawal: A Review of Neurobiological Mechanisms and Sex Differences. CURRENT ADDICTION REPORTS 2017; 4:75-81. [PMID: 29057200 PMCID: PMC5648025 DOI: 10.1007/s40429-017-0143-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW This report provides an updated overview of pre-clinical and clinical research on the etiology and biological substrates of the cannabis withdrawal syndrome. RECENT FINDINGS Long-term cannabis use is associated with downregulation of type-1 cannabinoid receptors (CB1). Reduced CB1 receptor density is related to increased withdrawal during early abstinence, and the reduction in CB1 receptor density reverses with extended abstinence. Females have been shown to have increased rate and severity of a subset of cannabis withdrawal symptoms compared with men. SUMMARY Recent studies have extended knowledge of the biological processes and individual difference variables that influence cannabis withdrawal. However, caveats include small sample sizes in clinical studies, participant samples that are predominantly male, and limited examinations of endocannabinoids, enzymes that degrade endocannabinoids, negative allosteric modulators, and other neurobiological systems that may directly impact cannabis withdrawal symptom expression.
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Affiliation(s)
- Nicolas J. Schlienz
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224
| | - Alan J. Budney
- Department of Psychiatry, Center for Technology and Behavioral Health, Geisel School of Medicine at Dartmouth, Lebanon, NH 03766
| | - Dustin C. Lee
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224
| | - Ryan Vandrey
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21224
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Abstract
The cannabis withdrawal syndrome (CWS) is a criterion of cannabis use disorders (CUDs) (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition) and cannabis dependence (International Classification of Diseases [ICD]-10). Several lines of evidence from animal and human studies indicate that cessation from long-term and regular cannabis use precipitates a specific withdrawal syndrome with mainly mood and behavioral symptoms of light to moderate intensity, which can usually be treated in an outpatient setting. Regular cannabis intake is related to a desensitization and downregulation of human brain cannabinoid 1 (CB1) receptors. This starts to reverse within the first 2 days of abstinence and the receptors return to normal functioning within 4 weeks of abstinence, which could constitute a neurobiological time frame for the duration of CWS, not taking into account cellular and synaptic long-term neuroplasticity elicited by long-term cannabis use before cessation, for example, being possibly responsible for cannabis craving. The CWS severity is dependent on the amount of cannabis used pre-cessation, gender, and heritable and several environmental factors. Therefore, naturalistic severity of CWS highly varies. Women reported a stronger CWS than men including physical symptoms, such as nausea and stomach pain. Comorbidity with mental or somatic disorders, severe CUD, and low social functioning may require an inpatient treatment (preferably qualified detox) and post-acute rehabilitation. There are promising results with gabapentin and delta-9-tetrahydrocannabinol analogs in the treatment of CWS. Mirtazapine can be beneficial to treat CWS insomnia. According to small studies, venlafaxine can worsen the CWS, whereas other antidepressants, atomoxetine, lithium, buspirone, and divalproex had no relevant effect. Certainly, further research is required with respect to the impact of the CWS treatment setting on long-term CUD prognosis and with respect to psychopharmacological or behavioral approaches, such as aerobic exercise therapy or psychoeducation, in the treatment of CWS. The up-to-date ICD-11 Beta Draft is recommended to be expanded by physical CWS symptoms, the specification of CWS intensity and duration as well as gender effects.
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Affiliation(s)
- Udo Bonnet
- Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Evangelisches Krankenhaus Castrop-Rauxel, Academic Teaching Hospital of the University of Duisburg-Essen, Castrop-Rauxel
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, LVR-Hospital Essen, University of Duisburg-Essen, Essen
| | - Ulrich W Preuss
- Vitos-Klinik Psychiatrie und Psychotherapie Herborn, Herborn
- Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
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Ramesh D, Schlosburg JE, Wiebelhaus JM, Lichtman AH. Marijuana dependence: not just smoke and mirrors. ILAR J 2016; 52:295-308. [PMID: 23382144 DOI: 10.1093/ilar.52.3.295] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Marijuana (Cannabis sativa) is the most commonly used illicit drug worldwide as well as in the Unites States. Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ9-tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals. The changes that occur with repeated cannabis use include alterations in behavioral, physiological, and biochemical responses. A variety of withdrawal responses occur in cannabis-dependent individuals: anger, aggression, irritability, anxiety and nervousness, decreased appetite or weight loss, restlessness, and sleep difficulties with strange dreams. But the long half-life and other pharmacokinetic properties of THC result in delayed expression of withdrawal symptoms, and because of the lack of contiguity between drug cessation and withdrawal responses the latter are not readily recognized as a clinically relevant syndrome. Over the past 30 years, a substantial body of clinical and laboratory animal research has emerged supporting the assertion that chronic exposure to cannabinoids produces physical dependence and may contribute to drug maintenance in cannabis-dependent individuals. However, no medications are approved to treat cannabis dependence and withdrawal. In this review, we describe preclinical and clinical research that supports the existence of a cannabinoid withdrawal syndrome. In addition, we review research evaluating potential pharmacotherapies (e.g., THC, a variety of antidepressant drugs, and lithium) to reduce cannabis withdrawal responses and examine how expanded knowledge about the regulatory mechanisms in the endocannabinoid system may lead to promising new therapeutic targets.
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Goldstein RB, Chou SP, Smith SM, Jung J, Zhang H, Saha TD, Pickering RP, Ruan WJ, Huang B, Grant BF. Nosologic Comparisons of DSM-IV and DSM-5 Alcohol and Drug Use Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III. J Stud Alcohol Drugs 2016; 76:378-88. [PMID: 25978823 DOI: 10.15288/jsad.2015.76.378] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE The purpose of this study was to examine prevalences and concordances between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and Fifth Edition (DSM-5) substance use disorders (SUDs) in a newly completed U.S. epidemiologic survey. METHOD The National Epidemiologic Survey on Alcohol and Related Conditions-III surveyed 36,309 civilian, noninstitutionalized adults. SUDs were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5. Concordances between DSM-IV and DSM-5 disorders were assessed using kappa statistics. RESULTS Prevalences of past-year substance-specific DSM-5 disorders (2+ criteria) were modestly higher than those of DSM-IV dependence and abuse combined for alcohol, sedatives/tranquilizers, opioids, and heroin, but lower for cannabis, cocaine, and stimulants. Lifetime prevalences were lower under DSM-5. Prevalences were similar between moderate to severe (4+ criteria) DSM-5 disorders and dependence, whereas prevalences of DSM-5 disorders at 3+ criteria (DSM-5 [3+]) were higher, particularly for cannabis. Past-year concordances were excellent for DSM-IV dependence and abuse combined versus any DSM-5 and DSM-IV dependence versus DSM-5 moderate to severe disorders; lifetime concordances were fair to excellent. Past-year concordances between DSM-IV and DSM-5 (3+) were generally similar to or modestly higher than those with any DSM-5 disorder; lifetime concordances were mostly lower. CONCLUSIONS Findings are consistent with those informing the development of DSM-5. Future research should examine differences in patterns between past-year and lifetime disorders, particularly for cannabis. Other questions warranting investigation include whether different combinations of the same numbers of criteria carry different clinical or nosologic implications, whether changes innosology yield changes in treatment demand, and whether changes in characteristics of individuals with DSM-5 SUDs dictate modifications to screening and intervention.
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Affiliation(s)
- Risë B Goldstein
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - S Patricia Chou
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - Sharon M Smith
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - Jeesun Jung
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - Haitao Zhang
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - Tulshi D Saha
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - Roger P Pickering
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - W June Ruan
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - Boji Huang
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
| | - Bridget F Grant
- Laboratory of Epidemiology and Biometry, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland
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User Experiences of Development of Dependence on the Synthetic Cannabinoids, 5f-AKB48 and 5F-PB-22, and Subsequent Withdrawal Syndromes. Int J Ment Health Addict 2016. [DOI: 10.1007/s11469-016-9650-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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Davis JP, Smith DC, Morphew JW, Lei X, Zhang S. Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study. JOURNAL OF DRUG ISSUES 2016; 46:64-83. [PMID: 26877548 PMCID: PMC4748964 DOI: 10.1177/0022042615616431] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use.
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Affiliation(s)
| | | | | | - Xinrong Lei
- University of Illinois at Urbana–Champaign, Urbana, IL, USA
| | - Saijun Zhang
- University of Illinois at Urbana–Champaign, Urbana, IL, USA
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Chauchard E, Goncharov O, Krupitsky E, Gorelick DA. Cannabis withdrawal in patients with and without opioid dependence. Subst Abus 2015; 35:230-4. [PMID: 24745656 DOI: 10.1080/08897077.2014.898605] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Cannabis use is common among opioid-dependent individuals, but little is known about cannabis withdrawal in this population. METHODS Thirty inpatients (57% men) completed the Marijuana Quit Questionnaire (MJQQ) after completing acute heroin detoxification treatment in Saint Petersburg, Russia. The MJQQ collected data on motivations for quitting, withdrawal symptoms, and coping strategies used to help maintain abstinence during their most "serious" (self-defined) quit attempt made without formal treatment outside a controlled environment. RESULTS At the start of their quit attempt, 70% of participants smoked cannabis at least weekly (40% daily), averaging [SD] 2.73 [1.95] joints daily; 60% were heroin dependent. Subjects with heroin dependence were significantly older at the start of their quit attempt (22.9 [3.6] vs. 19.1 [2.9] years), were significantly less likely to report withdrawal irritability/anger/aggression (22% vs. 58%), restlessness (0% vs. 25%), or physical symptoms (6% vs. 33%), or to meet diagnostic criteria for DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) cannabis withdrawal syndrome (6% vs. 33%), and had shorter duration of abstinence (29.6 [28.7] vs 73.7 [44.1] months) than those without heroin dependence. CONCLUSION Cannabis users with opioid dependence are less likely to experience cannabis withdrawal, suggesting that opiate use may prevent or mask the experience of cannabis withdrawal. RESULTS should be considered preliminary due to small convenience sample and retrospective data.
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Affiliation(s)
- Emeline Chauchard
- a Centre d'étude et de recherche en psychopathologie (CERPP) , Université de Toulouse-Le Mirail , Toulouse , France
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Benard V, Rolland B, Messaadi N, Petit A, Cottencin O, Karila L. [Cannabis use: what to do in general practice?]. Presse Med 2015; 44:707-15. [PMID: 26144274 DOI: 10.1016/j.lpm.2014.11.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Revised: 10/26/2014] [Accepted: 11/13/2014] [Indexed: 01/07/2023] Open
Abstract
Cannabis use is now more frequent than alcohol drinking or tobacco smoking among young people (15-34years), whereas it may induce numerous medical aftermaths. Identifying and assessing cannabis use in general practice have become a current public health issue. The two steps of screening consist in spotting risky use of cannabis, and then in checking criteria for cannabis use disorder (CUD). Risky use requires a "brief intervention" by the general practitioner (GP). In case of CUD, the new DSM-5 criteria allow measuring the severity of the subsequent disorder, and listing the medical and social consequences. Using these criteria can help the GP to decide when the patient should be referred to an addiction-specialized unit. The GP has also to spot the different physical and psychiatric complications of cannabis use, in order to coordinate care between the different specialists.
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Affiliation(s)
- Victoire Benard
- CHU de Lille, université Lille Nord de France, service d'addictologie, 59000 Lille, France
| | - Benjamin Rolland
- CHU de Lille, université Lille Nord de France, service d'addictologie, 59000 Lille, France
| | - Nassir Messaadi
- Université Lille Nord de France, département de médecine générale, 59000 Lille, France
| | - Aymeric Petit
- Hôpital universitaire Bichat-Claude Bernard, service d'addictologie, 75018 Paris, France
| | - Olivier Cottencin
- CHU de Lille, université Lille Nord de France, service d'addictologie, 59000 Lille, France
| | - Laurent Karila
- AP-HP, hôpital Paul-Brousse, université Paris Sud-11, centre d'enseignement, de recherche et de traitement des addictions, Inserm-CEA U1000, 94800 Villejuif, France.
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31
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The prevalence of cannabis withdrawal and its influence on adolescents' treatment response and outcomes: a 12-month prospective investigation. J Addict Med 2015; 8:359-67. [PMID: 25100311 DOI: 10.1097/adm.0000000000000064] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
BACKGROUND Withdrawal, a diagnostic indicator of cannabis use disorder, is often minimized or ignored as a consequence of cannabis use, particularly among adolescents. This study aims to characterize cannabis withdrawal among adolescents in outpatient treatment for substance use disorder and evaluate the clinical significance of withdrawal as a predictor of substance-related outcomes. METHODS Adolescent outpatients (N = 127) reporting cannabis as their drug of choice (n = 90) were stratified by the presence of withdrawal and compared on demographic and clinical variables at treatment intake. Hierarchical linear models compared the effect of withdrawal on percentage days abstinent (PDA) and related outcomes over a 1-year follow-up period. RESULTS Adolescents reporting withdrawal (40%) were more likely to meet criteria for cannabis dependence, have higher levels of substance use severity, report more substance-related consequences, and have a mood disorder. Withdrawal was not associated with PDA over the follow-up period; however, this relationship was moderated by problem recognition such that adolescents reporting withdrawal and a drug problem improved at a greater rate with respect to PDA than those who did not recognize a problem with drugs and did not report withdrawal. DISCUSSION Withdrawal is common among adolescent outpatients and is associated with a more clinically severe profile. In this sample, all adolescents reporting withdrawal met criteria for cannabis dependence, suggesting that withdrawal is a highly specific indicator of cannabis use disorder. Although withdrawal does not seem to be independently associated with substance use outcomes posttreatment, moderating factors such as drug problem recognition should be taken into account when formulating treatment and continuing care plans.
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Cousijn J, van Benthem P, van der Schee E, Spijkerman R. Motivational and control mechanisms underlying adolescent cannabis use disorders: A prospective study. Dev Cogn Neurosci 2015; 16:36-45. [PMID: 25922296 PMCID: PMC6989823 DOI: 10.1016/j.dcn.2015.04.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 03/27/2015] [Accepted: 04/01/2015] [Indexed: 01/23/2023] Open
Abstract
Adolescents with a CUD had an attentional but no approach bias towards cannabis. Cannabis craving significantly predicted cannabis use 6 months later. These findings identify craving as a predictor of treatment outcome. This study is among the first to investigate neuropsychological mechanisms underlying adolescent CUDs. Cannabis use disorders (CUDs) are the most prevalent substance use disorders among adolescents in treatment. Yet, little is known about the neuropsychological mechanisms underlying adolescent CUDs. Studies in adult cannabis users suggest a significant role for cognitive control and cannabis-oriented motivational processes, such as attentional bias, approach bias, and craving in CUDs. The current 6-month prospective study investigated the relationships between attentional bias, approach bias, craving, cognitive control, and cannabis use in adolescent patients in treatment for a primary or secondary CUD. Moreover, we investigated if these motivational processes and cognitive control could predict treatment progression after 6 months. Adolescents with a CUD had an attentional but no approach bias towards cannabis. In contrast to adult findings on the role of attentional bias, approach bias and cognitive control, only cannabis craving significantly correlated with current cannabis use and predicted cannabis use-related problems and abstinence from cannabis 6 months later. These findings identify craving as a predictor of treatment outcome, thereby supporting an important role for craving in the course of adolescent cannabis use and dependence. This prospective study is among the first to investigate neuropsychological mechanisms underlying adolescent CUDs, warranting future longitudinal studies.
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Affiliation(s)
- Janna Cousijn
- Consortium Individual Development, Departments of Developmental and Experimental Psychology, Utrecht University, Utrecht, The Netherlands; ADAPT-lab, Department of Developmental Psychology, University of Amsterdam, Amsterdam, The Netherlands.
| | - Patty van Benthem
- Parnassia Addiction Research Center (PARC), Brijder Addiction Care, The Hague, The Netherlands
| | - Evelien van der Schee
- Parnassia Addiction Research Center (PARC), Brijder Addiction Care, The Hague, The Netherlands
| | - Renske Spijkerman
- Parnassia Addiction Research Center (PARC), Brijder Addiction Care, The Hague, The Netherlands
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Abstract
Since its inception cannabis has been observed to be associated with various psycho-pathology. In this paper, the authors have reviewed the advancement made in this area over the last decade. The association between cannabis and schizophrenia has been researched more intensively. The controversy regarding the reliability, clinical utility, and the existence of a cannabis withdrawal syndrome has also been settled. Recent studies also buttressed the possibility of acute and chronic effect of cannabis on various cognitive functions. There has been a plethora of research regarding the treatment for cannabis use disorders. But the new and most interesting area of research is concentrated on the endocannabinoid system and its contribution in various psychiatric disorders.
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Affiliation(s)
- Abhishek Ghosh
- Department of Psychiatry, Drug De-addiction and Treatment Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Debasish Basu
- Department of Psychiatry, Drug De-addiction and Treatment Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Greydanus DE, Kaplan G, Baxter LE, Patel DR, Feucht CL. Cannabis: The never-ending, nefarious nepenthe of the 21st century: What should the clinician know? Dis Mon 2015; 61:118-75. [DOI: 10.1016/j.disamonth.2015.01.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Kelly SM, Gryczynski J, Mitchell SG, Kirk A, O’Grady KE, Schwartz RP. Concordance between DSM-5 and DSM-IV nicotine, alcohol, and cannabis use disorder diagnoses among pediatric patients. Drug Alcohol Depend 2014; 140:213-6. [PMID: 24793367 PMCID: PMC4070874 DOI: 10.1016/j.drugalcdep.2014.03.034] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 03/28/2014] [Accepted: 03/29/2014] [Indexed: 11/29/2022]
Abstract
BACKGROUND The recently published Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) includes several major revisions to substance use diagnoses. Studies have evaluated the impact of these changes among adult samples but research with adolescent samples is lacking. METHODS 525 adolescents (93% African American) awaiting primary care appointments in Baltimore, Maryland were recruited for a study evaluating a substance use screening instrument. Participants were assessed for DSM-5 nicotine, alcohol, and cannabis use disorder, DSM-IV alcohol and cannabis abuse, and DSM-IV dependence for all three substances during the past year using the modified Composite International Diagnostic Interview-2, Substance Abuse Module. Contingency tables examining DSM-5 vs. DSM-IV joint frequency distributions were examined for each substance. RESULTS Diagnoses were more prevalent using DSM-5 criteria compared with DSM-IV for nicotine (4.0% vs. 2.7%), alcohol (4.6% vs. 3.8%), and cannabis (10.7% vs. 8.2%). Cohen's κ, Somers' d, and Cramer's V ranged from 0.70 to 0.99 for all three substances. Of the adolescents categorized as "diagnostic orphans" under DSM-IV, 7/16 (43.8%), 9/29 (31.0%), and 13/36 (36.1%) met criteria for DSM-5 disorder for nicotine, alcohol, and cannabis, respectively. Additionally, 5/17 (29.4%) and 1/21 (4.8%) adolescents who met criteria for DSM-IV abuse did not meet criteria for a DSM-5 diagnosis for alcohol and cannabis, respectively. CONCLUSIONS Categorizing adolescents using DSM-5 criteria may result in diagnostic net widening-particularly for cannabis use disorders-by capturing adolescents who were considered diagnostic orphans using DSM-IV criteria. Future research examining the validity of DSM-5 substance use disorders with larger and more diverse adolescent samples is needed.
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Affiliation(s)
- Sharon M. Kelly
- Friends Research Institute, Inc., 1040 Park Avenue, Suite
103, Baltimore, MD 21201, USA,Corresponding author: Friends
Research Institute, Inc., 1040 Park Avenue, Suite 103, Baltimore, MD 21201, USA.
Tel.: +1 410 837 3977; Fax: +1 410 752 4218.
| | - Jan Gryczynski
- Friends Research Institute, Inc., 1040 Park Avenue, Suite
103, Baltimore, MD 21201, USA
| | - Shannon Gwin Mitchell
- Friends Research Institute, Inc., 1040 Park Avenue, Suite
103, Baltimore, MD 21201, USA
| | - Arethusa Kirk
- Total Health Care, 1501 Division Street, Baltimore, MD
21217, USA
| | - Kevin E. O’Grady
- Department of Psychology, University of Maryland, College
Park, MD 20742, USA
| | - Robert P. Schwartz
- Friends Research Institute, Inc., 1040 Park Avenue, Suite
103, Baltimore, MD 21201, USA
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Chesney T, Matsos L, Couturier J, Johnson N. Cannabis withdrawal syndrome: An important diagnostic consideration in adolescents presenting with disordered eating. Int J Eat Disord 2014; 47:219-23. [PMID: 24281745 DOI: 10.1002/eat.22229] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Revised: 10/11/2013] [Accepted: 11/01/2013] [Indexed: 11/10/2022]
Abstract
Although previously thought to have no withdrawal symptoms, there is now convergent evidence for a cannabis withdrawal syndrome (CWS), criteria for its diagnosis, and evidence of its impact in the adolescent population. Cannabis withdrawal syndrome represents an important and under-recognized consideration in adolescents with disordered eating. We describe three clinical cases of adolescents presenting to an eating disorders program with primary complaints of gastrointestinal symptoms, food avoidance, and associated weight loss. They did not meet the criteria for an eating disorder, but did fulfill the DSM-5 criteria for CWS. This report emphasizes the importance of considering the impact of heavy cannabis use in adolescents presenting with gastrointestinal complaints, and eating disorder symptoms, including weight loss.
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Abstract
BACKGROUND Cannabis is the most prevalent illicit drug in the world. Demand for treatment of cannabis use disorders is increasing. There are currently no pharmacotherapies approved for treatment of cannabis use disorders. OBJECTIVES To assess the effectiveness and safety of pharmacotherapies as compared with each other, placebo or supportive care for reducing symptoms of cannabis withdrawal and promoting cessation or reduction of cannabis use. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to 4 March 2014), MEDLINE (to week 3 February 2014), EMBASE (to 3 March 2014) and PsycINFO (to week 4 February 2014). We also searched reference lists of articles, electronic sources of ongoing trials and conference proceedings, and contacted selected researchers active in the area. SELECTION CRITERIA Randomised and quasi-randomised controlled trials involving the use of medications to reduce the symptoms and signs of cannabis withdrawal or to promote cessation or reduction of cannabis use, or both, in comparison with other medications, placebo or no medication (supportive care) in participants diagnosed as cannabis dependent or who were likely to be dependent. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by The Cochrane Collaboration. Two review authors assessed studies for inclusion and extracted data. All review authors confirmed the inclusion decisions and the overall process. MAIN RESULTS We included 14 randomised controlled trials involving 958 participants. For 10 studies the average age was 33 years; two studies targeted young people; and age data were not available for two studies. Approximately 80% of study participants were male. The studies were at low risk of selection, performance, detection and selective outcome reporting bias. Three studies were at risk of attrition bias.All studies involved comparison of active medication and placebo. The medications included preparations containing tetrahydrocannabinol (THC) (two studies), selective serotonin reuptake inhibitor (SSRI) antidepressants (two studies), mixed action antidepressants (three studies), anticonvulsants and mood stabilisers (three studies), an atypical antidepressant (two studies), an anxiolytic (one study), a norepinephrine reuptake inhibitor (one study) and a glutamatergic modulator (one study). One study examined more than one medication. Diversity in the medications and the outcomes reported limited the extent that analysis was possible. Insufficient data were available to assess the utility of most of the medications to promote cannabis abstinence at the end of treatment.There was moderate quality evidence that completion of treatment was more likely with preparations containing THC compared to placebo (RR 1.29, 95% CI 1.08 to 1.55; 2 studies, 207 participants, P = 0.006). There was some evidence that treatment with preparations containing THC was associated with reduced cannabis withdrawal symptoms and craving, but this latter outcome could not be quantified. For mixed action antidepressants compared with placebo (2 studies, 179 participants) there was very low quality evidence on the likelihood of abstinence from cannabis at the end of follow-up (RR 0.82, 95% CI 0.12 to 5.41), and moderate quality evidence on the likelihood of treatment completion (RR 0.93, 95% CI 0.71 to 1.21). For this same outcome there was very low quality evidence for the effects of SSRI antidepressants (RR 0.82, 95% CI 0.44 to 1.53; 2 studies, 122 participants), anticonvulsants and mood stabilisers (RR 0.78, 95% CI 0.42 to 1.46; 2 studies, 75 participants), and the atypical antidepressant, bupropion (RR 1.06, 95% CI 0.67 to 1.67; 2 studies, 92 participants). Available evidence on gabapentin (anticonvulsant) and N-acetylcysteine (glutamatergic modulator) was insufficient for quantitative estimates of their effectiveness, but these medications may be worth further investigation. AUTHORS' CONCLUSIONS There is incomplete evidence for all of the pharmacotherapies investigated, and for many of the outcomes the quality was downgraded due to small sample sizes, inconsistency and risk of attrition bias. The quantitative analyses that were possible, combined with general findings of the studies reviewed, indicate that SSRI antidepressants, mixed action antidepressants, atypical antidepressants (bupropion), anxiolytics (buspirone) and norepinephrine reuptake inhibitors (atomoxetine) are probably of little value in the treatment of cannabis dependence. Preparations containing THC are of potential value but, given the limited evidence, this application of THC preparations should be considered still experimental. Further studies should compare different preparations of THC, dose and duration of treatment, adjunct medications and therapies. The evidence base for the anticonvulsant gabapentin and the glutamatergic modulator N-acetylcysteine is weak, but these medications are also worth further investigation.
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Affiliation(s)
- Kushani Marshall
- Discipline of Pharmacology, University of Adelaide, Adelaide, Australia
| | - Linda Gowing
- Discipline of Pharmacology, University of Adelaide, Adelaide, Australia
| | - Robert Ali
- Discipline of Pharmacology, University of Adelaide, Adelaide, Australia
| | - Bernard Le Foll
- Translational Addiction Research Laboratory, Centre for Addiction and Mental Health ; University of Toronto, Toronto, Canada
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Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers. BMC Psychiatry 2013; 13:258. [PMID: 24118963 PMCID: PMC4015312 DOI: 10.1186/1471-244x-13-258] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2012] [Accepted: 10/10/2013] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco use. METHODS Symptoms of withdrawal were assessed through patient self-reports during detoxification in Danish residential rehabilitation centers. Patients (n = 90) completed booklets three times during their first month at the treatment centre. Self-reported withdrawal symptoms was rated using the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity. RESULTS With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams. CONCLUSIONS The findings yield strong support to the notion of a cannabis withdrawal syndrome, and gives further evidence for the inclusion of the criterion of vivid, unpleasant dreams. Further, the findings speak against the significance of demand characteristics in determining the course of the symptoms of cannabis withdrawal.
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Hasin DS, O’Brien CP, Auriacombe M, Borges G, Bucholz K, Budney A, Compton WM, Crowley T, Ling W, Petry NM, Schuckit M, Grant BF. DSM-5 criteria for substance use disorders: recommendations and rationale. Am J Psychiatry 2013; 170:834-51. [PMID: 23903334 PMCID: PMC3767415 DOI: 10.1176/appi.ajp.2013.12060782] [Citation(s) in RCA: 877] [Impact Index Per Article: 73.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Since DSM-IV was published in 1994, its approach to substance use disorders has come under scrutiny. Strengths were identified (notably, reliability and validity of dependence), but concerns have also arisen. The DSM-5 Substance-Related Disorders Work Group considered these issues and recommended revisions for DSM-5. General concerns included whether to retain the division into two main disorders (dependence and abuse), whether substance use disorder criteria should be added or removed, and whether an appropriate substance use disorder severity indicator could be identified. Specific issues included possible addition of withdrawal syndromes for several substances, alignment of nicotine criteria with those for other substances, addition of biomarkers, and inclusion of nonsubstance, behavioral addictions.This article presents the major issues and evidence considered by the work group, which included literature reviews and extensive new data analyses. The work group recommendations for DSM-5 revisions included combining abuse and dependence criteria into a single substance use disorder based on consistent findings from over 200,000 study participants, dropping legal problems and adding craving as criteria, adding cannabis and caffeine withdrawal syndromes, aligning tobacco use disorder criteria with other substance use disorders, and moving gambling disorders to the chapter formerly reserved for substance-related disorders. The proposed changes overcome many problems, while further studies will be needed to address issues for which less data were available.
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The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Drug Alcohol Depend 2013; 128:64-70. [PMID: 22921474 PMCID: PMC3546149 DOI: 10.1016/j.drugalcdep.2012.08.001] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2012] [Revised: 07/19/2012] [Accepted: 08/01/2012] [Indexed: 11/22/2022]
Abstract
BACKGROUND Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. METHODS Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. RESULTS Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. CONCLUSIONS Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted.
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Gorelick DA, Levin KH, Copersino ML, Heishman SJ, Liu F, Boggs DL, Kelly DL. Diagnostic criteria for cannabis withdrawal syndrome. Drug Alcohol Depend 2012; 123:141-7. [PMID: 22153944 PMCID: PMC3311695 DOI: 10.1016/j.drugalcdep.2011.11.007] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2011] [Revised: 10/27/2011] [Accepted: 11/01/2011] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Cannabis withdrawal occurs in frequent users who quit, but there are no accepted diagnostic criteria for a cannabis withdrawal syndrome (CWS). This study evaluated diagnostic criteria for CWS proposed in DSM-V and two earlier proposals. METHOD A convenience sample of 384 adult, non-treatment-seeking lifetime cannabis smokers provided retrospective self-report data on their "most difficult" quit attempt without formal treatment, which was used in this secondary analysis. Prevalence, time of onset, and peak intensity (5-point Likert scale) for 39 withdrawal symptoms (drawn from the literature) were assessed via computer-administered questionnaire. Subject groups were compared using chi-square or ANOVA. Symptom clustering was evaluated with principal components analysis. RESULTS 40.9% of subjects met the DSM-V criterion of ≥3 symptoms from a list of 7. There were no associations with sex, race, or type of cannabis preparation used. There were significant positive associations between duration or frequency of cannabis use prior to the quit attempt and experiencing CWS. Subjects with CWS had a significantly shorter duration of abstinence. Alternative syndromal criteria (dropping physical symptoms from DSM-V list; requiring ≥2 or ≥4 symptoms from a list of 11) yielded a similar prevalence of CWS and similar associations with prior cannabis use and relapse. The PCA yielded 12 factors, including some symptom clusters not included in DSM-V. CONCLUSIONS Findings support the concurrent and predictive validity of the proposed DSM-V CWS, but suggest that the list of withdrawal symptoms and number required for diagnosis warrant further evaluation.
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Affiliation(s)
- David A Gorelick
- Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
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Stewart JL, McMahon LR. The fatty acid amide hydrolase inhibitor URB 597: interactions with anandamide in rhesus monkeys. Br J Pharmacol 2012; 164:655-66. [PMID: 21449917 DOI: 10.1111/j.1476-5381.2011.01388.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND AND PURPOSE The fatty acid amide hydrolase inhibitor URB 597 increases brain anandamide levels, suggesting that URB 597 could enhance the behavioural effects of anandamide. The goal of the current study was to examine and characterize the in vivo pharmacology of URB 597 alone and in combination with anandamide and Δ⁹-tetrahydrocannabinol (Δ⁹ -THC) in two drug discrimination assays in rhesus monkeys. EXPERIMENTAL APPROACH The effects of URB 597 alone and in combination with anandamide were investigated in one group of monkeys (n= 4) that discriminated Δ⁹-THC (0.1 mg·kg⁻¹ i.v.) from vehicle, and in another group (n= 5) receiving chronic Δ⁹-THC (1 mg·kg⁻¹ 12 h⁻¹ s.c.) that discriminated the cannabinoid antagonist rimonabant (1 mg·kg⁻¹ i.v.). KEY RESULTS Intravenous anandamide fully substituted for, and had infra-additive effects with, Δ⁹-THC. URB 597 (up to 3.2 mg·kg⁻¹ i.v.) did not substitute for or modify the effects of Δ⁹-THC but markedly increased the potency (32-fold) and duration of action of anandamide. The rimonabant discriminative stimulus in Δ⁹-THC-treated monkeys (i.e. Δ⁹-THC withdrawal) was attenuated by both Δ⁹-THC (at doses larger than 1 mg·kg⁻¹ per 12 h) and anandamide but not by URB 597 (3.2 mg·kg⁻¹). URB 597 did not increase the potency of anandamide to attenuate the rimonabant-discriminative stimulus. CONCLUSIONS AND IMPLICATIONS URB 597 enhanced the behavioural effects of anandamide but not other CB₁ agonists. However, URB 597 did not significantly enhance the attenuation of Δ⁹-THC withdrawal induced by anandamide. Collectively, these data suggest that endogenous anandamide in primate brain does not readily mimic the behavioural effects of exogenously administered anandamide.
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Affiliation(s)
- Jennifer L Stewart
- Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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Morley KC, Haber PS, Morgan ML, Samara F. Pericyazine in the treatment of cannabis dependence in general practice: a naturalistic pilot trial. Subst Abuse Rehabil 2012; 3:43-7. [PMID: 24474865 PMCID: PMC3886674 DOI: 10.2147/sar.s30052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Cannabis is one of the most widely used illicit drugs worldwide. However, while the rates of cannabis dependence and treatment increase, there remains no medications approved for this use. Due to its sedative effects and low abuse liability, the typical antipsychotic pericyazine has been utilized in some parts of Australia for the treatment of cannabis dependence. We aimed to provide documentation of preliminary outcomes and acceptability of pericyazine treatment in a small sample. A naturalistic case series study was conducted in which 21 patients were enrolled for a 4-week course of pericyazine (up to 8 × 2.5 mg tablets daily) and weekly medical review. Levels of cannabis use were reported and side effects with electrocardiography and blood tests were monitored. Measures of dependence severity, depression, anxiety, and insomnia were taken at baseline and follow-up utilizing validated psychometric tools. Significant reductions in cannabis use, depression, anxiety, and insomnia severity occurred across time. Pericyazine appeared to be well tolerated and easily administered in the community clinics. The results provide some preliminary evidence that low-dose short-term pericyazine may be an acceptable mode of treatment in this population. Given the open-label nature of the design, we cannot conclude that pharmacotherapy was uniquely responsible for the treatment effect. Nonetheless, low-dose pericyazine may be a potentially effective approach to the treatment of cannabis dependence, and further evaluation via a randomized placebo-controlled trial is warranted.
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Affiliation(s)
- Kirsten C Morley
- Discipline of Addiction Medicine, Sydney Medical School, University of Sydney, NSW, Australia
| | - Paul S Haber
- Discipline of Addiction Medicine, Sydney Medical School, University of Sydney, NSW, Australia ; Drug Health Services, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
| | - Madeleine L Morgan
- Drug and Alcohol Services, North Coast Area Health Service, Kempsey and Port Macquarie, NSW, Australia
| | - Fares Samara
- Drug and Alcohol Services, North Coast Area Health Service, Kempsey and Port Macquarie, NSW, Australia ; Durri Aboriginal Medical Service, Kempsey, NSW, Australia
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[Cannabis withdrawal syndrome in patients with cannabis dependence only, and in patients with cannabis and opioid dependence]. Encephale 2011; 37:266-72. [PMID: 21981886 DOI: 10.1016/j.encep.2010.12.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2010] [Accepted: 09/14/2010] [Indexed: 11/21/2022]
Abstract
BACKGROUND The cannabis withdrawal syndrome occurs after cannabis cessation in more than 50% of dependent smokers. But although opioid-dependent patients are more frequently cannabis users and cannabis-dependent than the general population, the frequency and phenomenology of cannabis withdrawal symptoms in this specific population is unknown. Our hypothesis was that cannabis-dependent patients with current opioid dependence would experience the same withdrawal syndrome after cannabis cessation. OBJECTIVE To describe cannabis withdrawal symptoms in cannabis-only dependent patients and in cannabis-dependent patients with current opioid dependence. METHODS Using retrospective interviews, we evaluated the number and duration of six cannabis withdrawal symptoms in two groups: 56 cannabis-dependent patients without and 43 cannabis dependent patients with current opioid dependence. Cannabis and opioid dependence diagnoses were defined with DSM IV criteria using the MINI structured interview. RESULTS The two groups were not different in terms of age of onset of cannabis use, and number of cannabis joints smoked at the time of the cannabis cessation attempt. The frequency of a cannabis withdrawal syndrome (defined as at least two different symptoms) did not differ in the two groups (65%). Neither was the proportion of subjects with the following symptoms: appetite or weight loss (30.8%), irritability (45.1%), anxiety (56%), aggression (36.3%) and restlessness (45.1%). Patients with cannabis dependence and current opioid dependence were more likely to report sleep disturbances (79.1 vs. 53.6%, chi(2)=6.91, P=0.007). The median duration of this cannabis withdrawal syndrome was 20 days post-cessation. CONCLUSION This is, to our knowledge, the first study describing cannabis withdrawal syndrome in cannabis-dependent patients with current opioid dependence. These patients experience a cannabis withdrawal syndrome as often as cannabis-only dependent subjects, but describe more frequently sleep disturbances. This high rate of sleep disturbances may cause relapse to cannabis use.
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Marshall KS, Gowing L, Ali R. Pharmacotherapies for cannabis withdrawal. THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS 2011. [DOI: 10.1002/14651858.cd008940] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers. Drug Alcohol Depend 2010; 111:120-7. [PMID: 20510550 PMCID: PMC2930056 DOI: 10.1016/j.drugalcdep.2010.04.010] [Citation(s) in RCA: 110] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2009] [Revised: 04/08/2010] [Accepted: 04/11/2010] [Indexed: 11/24/2022]
Abstract
BACKGROUND Cannabis withdrawal is not recognized in DSM-IV because of doubts about its clinical significance. OBJECTIVES Assess the phenomenon of cannabis withdrawal and its relationship to relapse in non-treatment-seeking adults. SUBJECTS Convenience sample of 469 adult cannabis smokers who had made a quit attempt while not in a controlled environment. METHODS Subjects completed a 176-item Marijuana Quit Questionnaire collecting information on sociodemographic characteristics, cannabis use history, and their "most difficult" cannabis quit attempt. RESULTS 42.4% of subjects had experienced a lifetime withdrawal syndrome, of whom 70.4% reported using cannabis in response to withdrawal. During the index quit attempt, 95.5% of subjects reported > or =1 individual withdrawal symptom (mean [SD] 9.5 [6.1], median 9.0); 43.1% reported > or =10. Number of withdrawal symptoms was significantly associated with greater frequency and amount of cannabis use, but symptoms occurred even in those using less than weekly. Symptoms were usually of > or = moderate intensity and often prompted actions to relieve them. Alcohol (41.5%) and tobacco (48.2%) were used more often than cannabis (33.3%) for this purpose. There was little change during withdrawal in use of other legal or illegal substances. CONCLUSIONS Cannabis withdrawal is a common syndrome among adults not seeking treatment. The intention to relieve withdrawal symptoms can drive relapse during quit attempts, giving cannabis withdrawal clinical significance as a target of treatment.
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Current world literature. Addictive disorder. Curr Opin Psychiatry 2009; 22:331-6. [PMID: 19365188 DOI: 10.1097/yco.0b013e32832ae253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Moreira FA, Grieb M, Lutz B. Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression. Best Pract Res Clin Endocrinol Metab 2009; 23:133-44. [PMID: 19285266 DOI: 10.1016/j.beem.2008.09.003] [Citation(s) in RCA: 209] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Both agonists (e.g. Delta(9)-tetrahydrocannabinol, nabilone) and antagonists (e.g. rimonabant, taranabant) of the cannabinoid type-1 (CB(1)) receptor have been explored as therapeutic agents in diverse fields of medicine such as pain management and obesity with associated metabolic dysregulation, respectively. CB(1) receptors are widely distributed in the central nervous system and are involved in the modulation of emotion, stress and habituation responses, behaviours that are thought to be dysregulated in human psychiatric disorders. Accordingly, CB(1) receptor activation may, in some cases, precipitate episodes of psychosis and panic, while its inhibition may lead to behaviours reminiscent of depression and anxiety-related disorders. The present review discusses these side-effects, which have to be taken into account in the therapeutic exploitation of the endocannabinoid system.
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Affiliation(s)
- Fabrício A Moreira
- Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 6, 55099 Mainz, Germany
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Martin CS, Chung T, Langenbucher JW. How should we revise diagnostic criteria for substance use disorders in the DSM-V? JOURNAL OF ABNORMAL PSYCHOLOGY 2008; 117:561-75. [PMID: 18729609 DOI: 10.1037/0021-843x.117.3.561] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
This article reviews literature on the validity and performance characteristics of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) diagnostic criteria for substance use disorders (SUDs) and recommends changes in these criteria that should be considered for the next edition of the DSM (DSM-V). Substantial data indicate that DSM-IV substance abuse and substance dependence are not distinct categories and that SUD criteria are best modeled as reflecting a unidimensional continuum of substance-problem severity. The conceptually and empirically problematic substance abuse diagnosis should be abandoned in the DSM-V, with substance dependence defined by a single set of criteria. Data also indicate that various individual SUD criteria should be revised, dropped, or considered for inclusion in the DSM-V. The DSM-V should provide a framework that allows the integration of categorical and dimensional approaches to diagnosis. Important areas for further research are noted.
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Affiliation(s)
- Christopher S Martin
- Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
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