Cannabidiol Cigarettes as Adjunctive Treatment for Psychotic Disorders – A Randomized, Open-Label Pilot-Study

Background: Psychotic disorders are associated with high rates of comorbid substance use disorders. Use of cannabis rich in tetrahydrocannabinol (THC) is linked to an increased risk of psychosis, worsening of psychotic symptoms, and an adverse course of psychotic disorders. Previous studies suggest oral cannabidiol (CBD) as possible novel antipsychotic agent; however, no studies evaluated the effects of smoked CBD.Objective: The main aim of the study was to clarify the antipsychotic potential of CBD used as adjunctive therapy simulating a naturalistic setting. Our trial is the first study evaluating the effects of smoked CBD-cigarettes as adjunctive therapy for psychotic symptoms.Methods: A randomized, placebo-controlled open-label trial of cigarettes containing CBD-rich cannabis (THC < 1%) as adjunctive therapy to standard psychiatric treatment was conducted (ClinicalTrials.gov identifier NCT04700930). Primary outcomes were mean scores of Positive and Negative Syndrome Scale (PANSS), Brøset Violence Checklist, the Beck's Depression Inventory (BDI), the Subjective Well-Being Under Neuroleptics Scale short form (SWN-K), and antipsychotic medication equivalent doses. Outcomes were assessed after 4 weeks of acute treatment and long-term follow-up after discontinuation of CBD-cigarettes after 25 weeks. Participants were 31 acutely psychotic patients with tobacco use disorder and a mean age of 35.1 ± 10.58 years (71% male). Comorbid cannabis use was diagnosed in 51.6%.Results: A discontinuous multilevel model revealed no significant group differences for primary outcomes. After 4 weeks of acute treatment, mean PANSS and BDI decreased in both groups, while an increase of antipsychotic medication equivalent was observed in the placebo group.Conclusions: The presented findings might suggest an antipsychotic medication sparing effect of CBD-cigarettes as adjunctive treatment of acute psychosis. However, the low number of participants did not allow for further statistical analysis. Hence, a larger study sample and a more rigorous study design (blinding of the interventional product, fixed dosing regimen) may reveal different results.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04700930

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Perceived functioning, well-being and psychiatric symptoms in patients with stable schizophrenia treated with long-acting risperidone for 1 year

The British Journal of Psychiatry ◽

10.1192/bjp.187.2.131 ◽

2005 ◽

Vol 187 (2) ◽

pp. 131-136 ◽

Cited By ~ 63

Author(s):

W. Wolfgang Fleischhacker ◽

Jonathan Rabinowitz ◽

Georg Kemmler ◽

Mariëlle Eerdekens ◽

Angelika Mehnert

Keyword(s):

Mental Component Summary ◽

Psychiatric Symptoms ◽

Short Form ◽

Mental Component Summary Score ◽

Well Being ◽

Psychotic Symptoms ◽

Open Label ◽

Sf 36 ◽

Patient Reported ◽

Long Acting

BackgroundThe extent to which antipsychotics improve patients' well-being is uncertain.AimsTo examine psychopathology and patient-rated functioning and well-being in patients treated with risperidone.MethodIn a 1-year, open-label, international multicentre trial of long-acting risperidone in 615 stable adult patients with schizophrenia, self-rated functioning and well-being were measured every 3 months using the Short Form 36-item questionnaire (SF–36). Psychopathology was quantified using the Positive and Negative Syndrome Scale (PANSS).ResultsSignificant improvements were found on the SF–36 mental component summary score and vitality and social functioning scales. PANSS and mental component summary scores were moderately correlated.ConclusionsPatient-reported functioning and well-being appear to differ from investigator-rated psychotic symptoms. Patient-rated well-being should be assessed with symptoms to help measure treatment outcomes.

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Associations between childhood trauma, bullying and psychotic symptoms among a school-based adolescent sample

The British Journal of Psychiatry ◽

10.1192/bjp.bp.108.049536 ◽

2008 ◽

Vol 193 (5) ◽

pp. 378-382 ◽

Cited By ~ 155

Author(s):

Ian Kelleher ◽

Michelle Harley ◽

Fionnuala Lynch ◽

Louise Arseneault ◽

Carol Fitzpatrick ◽

...

Keyword(s):

Domestic Violence ◽

High Risk ◽

Childhood Trauma ◽

Psychotic Disorders ◽

Traumatic Events ◽

High Risk Group ◽

Traumatic Experiences ◽

Psychotic Symptoms ◽

High Risk Population ◽

Increased Risk

BackgroundChildren and adolescents who report psychotic symptoms appear to be at increased risk for psychotic disorders in adulthood – a putative ‘symptomatic’ high-risk group. However, little research has investigated whether those in this high-risk population have increased rates of exposure to traumatic events in childhood, as seen in patients who have a psychotic illness.AimsTo examine whether adolescents with psychotic symptoms have an increased rate of traumatic experiences.MethodPsychiatric interviews were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about a number of early traumatic events including physical and sexual abuse, exposure to domestic violence and bullying.ResultsFourteen adolescents (6.6% of those interviewed) reported experiencing at least one psychotic symptom. Adolescents who reported psychotic symptoms were significantly more likely to have been physically abused in childhood, to have been exposed to domestic violence and to be identified as a bully/victim (that is, both a perpetrator and victim of bullying) than those who did not report such symptoms. These findings were not confounded by comorbid psychiatric illness or family history of psychiatric history.ConclusionsOur findings suggest that childhood trauma may increase the risk of psychotic experiences. The characteristics of bully/victims deserve further study.

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A phase III study of xilonix in refractory colorectal cancer patients with weight loss.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.685 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 685-685 ◽

Cited By ~ 2

Author(s):

George A. Fisher

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Human Monoclonal Antibody ◽

Well Being ◽

Phase Iii ◽

Controlled Study ◽

Open Label ◽

Risk Of Death ◽

Increased Risk ◽

Median Change

685 Background: Xilonix, an anti-interleukin-1α true human monoclonal antibody is being assessed as cancer therapy to improve overall survival (OS) in advanced colorectal cancer (CRC) patients. Methods: An open label multicenter randomized comparator controlled study to evaluate efficacy and safety of Xilonix in CRC complicated with cachexia. Eligible patients had metastatic CRC, failed oxaliplatin or irinotecan based chemotherapy, and lost ≥5% total body weight in the previous 6 months (m). Patients were 1:1 randomized to Xilonix (3.75 mg/kg intravenously every two weeks) or megestrol acetate (MA, oral 800 mg daily) until progression. Primary endpoint was OS. Secondary endpoints included assessment of patient well-being using the EORTC QLQ-C30 questionnaire. Platelets support tumor growth and metastasis and platelet counts increase during cancer progression. IL-1α on platelets may be a target of Xilonix and thus platelet count was a key pharmacodynamic measure. Results: 40 patients were enrolled between March 2013 and July 2014, at which time the study was halted to revise inclusion criteria to reduce screen failures. An eligibility violation excluded 1 Xilonix patient from analysis (Xilonix n=19, MA n=20). MA treatment arm had a 39% shorter median OS (2.0 versus 2.8 months) and a trend in increased risk of death (hazard ratio 2.17, p=0.17). Physical and role function worsened in patients receiving megesterol (median change of -13.3 (p=0.02), -16.7 (p=0.02) respectively), whereas in Xilonix treated patients these functions did not decline during therapy (median change 0, p=0.88 and 0, p=0.69, respectively). Xilonix patients had treatment-related reduction in platelets compared to the MA group (median -60,000/mm3, vs 10,000/mm3, p=0.03). No infusion reactions, no discontinuations due to adverse events (AEs) and no related SAEs were reported for Xilonix. Conclusions: The trend in OS for Xilonix patients was encouraging and consistent with improved function and intended pharmacodynamic activity. An amended Phase III protocol has been developed to simplify enrollment for an ongoing study of Xilonix in an advanced CRC population. (NCT01767857) Clinical trial information: NCT01767857.

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Thoughts on the behavioural phenotypes in Prader-Willi syndrome and velo-cardio-facial syndrome: a novel approach

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2007.00202.x ◽

2007 ◽

Vol 19 (4) ◽

pp. 244-250 ◽

Cited By ~ 8

Author(s):

Willem Verhoeven ◽

Jos Egger ◽

Siegfried Tuinier

Keyword(s):

Psychotic Disorders ◽

Bipolar Affective Disorder ◽

Probabilistic Approach ◽

Deletion Syndrome ◽

Psychotic Symptoms ◽

Prader Willi Syndrome ◽

Behavioural Phenotype ◽

Genetic Syndrome ◽

Increased Risk ◽

Velo Cardio Facial Syndrome

Background:In both Prader-Willi syndrome (PWS) and 22q11 deletion syndrome [velo-cardio-facial syndrome (VCFS)], an increased risk for psychotic disorders is reported, which are as a rule not included in the behavioural phenotype of these two syndromes. For the description of a behavioural phenotype, the complete spectrum of physical, developmental, neuropsychological and psychiatric aspects is generally not taken into account. Moreover, psychiatric signs and symptoms often do not meet the criteria for a categorical diagnosis.Objective:In this study, a further specification of psychotic symptoms in PWS and VCFS is shown as well as a proposal for a new model to ascertain predictors, including behavioural, for a genetic syndrome.Methods:Over the past years, 27 patients with PWS and 19 with VCFS were referred for neuropsychiatric evaluation because of psychotic symptoms. In all the patients, a standardised psychiatric examination was performed; seven of the patients with VCFS were evaluated by means of an extensive neuropsychological battery.Results:In both patient groups, a rather specific psychopathological profile seemed to be present, which in the case of patients with PWS showed some resemblance with bipolar affective disorder. In patients with VCFS, no formal psychiatric diagnosis could be established. Because the psychopathological profiles were rather aspecific, they are not sufficient to predict membership of a certain syndrome.Conclusions:A quantitative probabilistic approach toward the description of a (behavioural) phenotype is suggested. For such a procedure, large data sets and international collaboration are required.

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Case Report: CBD Cigarettes for Harm Reduction and Adjunctive Therapy in a Patient With Schizophrenia and Substance Use Disorder

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.712110 ◽

2021 ◽

Vol 12 ◽

Author(s):

Maximilian Meyer ◽

Marc Walter ◽

Stefan Borgwardt ◽

Alexandra Scheidegger ◽

Elisabeth Lang ◽

...

Keyword(s):

Substance Use ◽

Case Report ◽

Substance Use Disorder ◽

Adjunctive Therapy ◽

Cannabis Sativa ◽

Psychotic Symptoms ◽

Course Of Disease ◽

Increased Risk ◽

Patient Reported ◽

Continued Use

The treatment of patients with schizophrenia and substance use disorder poses a challenge for clinicians. Continued use of cannabis and cocaine can exacerbate psychotic symptoms and worsen the course of disease. To date, no pharmacotherapy is available for patients with cannabis use disorder (CUD). Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the main active constituents in Cannabis sativa, with the latter being linked to an increased risk of psychosis. We describe a clinical case of a male patient diagnosed with schizophrenia, combined personality disorder, CUD and cocaine use disorder. Over the course of 8 years, he was hospitalized 30 times due to psychotic relapses and continued substance use. Consequently, CBD cigarettes with a low THC content (<1%) were used as adjunctive therapy. Additionally, we established off-label treatment with methylphenidate to support abstinence. The patient reported to feel significantly less need to consume illegal cannabis with a high THC content. He stopped to use cocaine, for the time being, and has not been hospitalized since. This case report demonstrates the potential of smoked CBD as a substitute for severe and chronic CUD.

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Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study

Psychological Medicine ◽

10.1017/s0033291706008774 ◽

2006 ◽

Vol 36 (11) ◽

pp. 1541-1550 ◽

Cited By ~ 302

Author(s):

PAUL FEARON ◽

JAMES B. KIRKBRIDE ◽

CRAIG MORGAN ◽

PAOLA DAZZAN ◽

KEVIN MORGAN ◽

...

Keyword(s):

Ethnic Minority ◽

Psychotic Disorders ◽

Minority Groups ◽

Age Groups ◽

Incidence Rates ◽

Psychotic Symptoms ◽

Ethnic Minority Groups ◽

Black Africans ◽

Increased Risk ◽

Rate Ratios

Background. The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk.Method. We identified all people (n=568) aged 16–64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated.Results. We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9·1, manic psychosis 8·0) and Black Africans (schizophrenia 5·8, manic psychosis 6·2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study.Conclusions. Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.

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Prevalence and associated risk factors of psychotic symptoms in homeless people in France

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.303 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S341-S341

Author(s):

A. Tortelli ◽

F. Perquier ◽

V. Le Masson ◽

D. Sauze ◽

N. Skurnik ◽

...

Keyword(s):

Sexual Abuse ◽

General Population ◽

Childhood Abuse ◽

Early Life ◽

Psychotic Disorders ◽

Homeless People ◽

Psychotic Symptoms ◽

Psychological Violence ◽

Increased Risk ◽

Significant Difference

IntroductionHomeless people are more likely to have higher prevalence of psychotic disorders than general population. However, we know less about the prevalence of psychotic symptoms in this group.ObjectivesTo estimate the lifetime and current prevalence of psychotic symptoms and their correlates among homeless people living in the Paris metropolitan area.MethodsWe analysed data from 839 homeless randomly selected for the “Samenta” survey that studied mental health and addiction problems in this population. The mini-international neuropsychiatric interview was used to assess psychotic symptoms. Separate multivariate logistic regression analyses were conducted to estimate the associations of sociodemographic characteristics (age, gender, education level and migrant status), early life experiences (sexual abuse, physical and psychological violence, substance use) and psychiatric disorders.ResultsThe lifetime prevalence of psychotic symptoms was 35.4% (95% CI = 28.1–43.5) and the prevalence of current symptoms was 14,0% (95% CI = 9,8–19,6) with no significant difference between migrant and native groups, after exclusion of subjects with a diagnosis of psychotic disorder (n = 145). In multi-adjusted models, childhood sexual abuse was associated with an increased risk of lifetime or current psychotic symptoms (OR > 4, P < 0.05). Early life psychological violence was strongly associated with the risk of lifetime psychotic symptoms in natives (OR = 6.33; 95% CI = 2.10–19.0), whereas alcohol misuse in adolescence was related to lifetime or current psychotic symptoms in migrants (OR = 3.34; 95% CI = 1.20–9.37).ConclusionHomeless people are at higher risk of psychotic symptoms compared to the general population in France. Our findings are consistent with the hypothesis that childhood abuse is an important risk factor of the psychosis continuum.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Change in cannabis use, clinical symptoms and social functioning among patients with first-episode psychosis: a 5-year follow-up study of patients in the OPUS trial

Psychological Medicine ◽

10.1017/s0033291713000433 ◽

2013 ◽

Vol 44 (1) ◽

pp. 117-126 ◽

Cited By ~ 30

Author(s):

L. Clausen ◽

C. R. Hjorthøj ◽

A. Thorup ◽

P. Jeppesen ◽

L. Petersen ◽

...

Keyword(s):

Antipsychotic Medication ◽

Negative Symptoms ◽

Psychotic Disorders ◽

Clinical Symptoms ◽

First Episode Psychosis ◽

Cannabis Use ◽

Psychotic Symptoms ◽

First Episode ◽

Episode Psychosis

BackgroundSeveral studies indicate that cannabis use among patients with psychotic disorders is associated with worse outcome, but only a few studies have controlled for baseline condition and medication.MethodAt 5-year follow-up, interviews were carried out with 314 first-episode psychosis patients included in the OPUS trial. The patients included were in the age range of 18 to 45 years old and 59% were male. Cannabis use was extracted from the Schedule for Clinical Assessment in Neuropsychiatry. At follow-up, the patients were divided into different groups according to the variable cannabis use: abstainers, stoppers, starters and continuers. Psychotic, negative and disorganized dimensions (ranging from zero to five) were calculated for each of the four groups based on the Schedule for the Assessment of Positive and Negative Symptoms in Schizophrenia.ResultsCannabis users were younger (24.6 years v. 27.4 years, p < 0.001) and had a lower level of education. At the 5-year follow-up, users of cannabis had higher scores on the psychotic dimension [difference 0.97, 95% confidence interval (CI) 0.41–1.53, p = 0.001] and lower levels of the Global Assessment of Functioning (difference 8.26, 95% CI 2.13–14.39, p = 0.01). Those who stopped using cannabis between entry and 5-year follow-up had a significantly lower level of psychotic symptoms at 5-year follow-up even after controlling for baseline level of psychotic symptoms and for insufficient antipsychotic medication (adjusted difference in psychotic dimension –1.04, 95% CI –1.77 to –0.31, p = 0.006).ConclusionsContinuous cannabis use was associated with higher levels of psychotic symptoms after 5 years, and this association was only partly explained by insufficient antipsychotic medication.

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Ethnic minority position and migrant status as risk factors for psychotic symptoms in the general population: a meta-analysis

Psychological Medicine ◽

10.1017/s0033291718002271 ◽

2018 ◽

Vol 49 (4) ◽

pp. 545-558 ◽

Cited By ~ 12

Author(s):

Edouard Leaune ◽

Marie-Jose Dealberto ◽

David Luck ◽

Stéphanie Grot ◽

Halima Zeroug-Vial ◽

...

Keyword(s):

General Population ◽

Ethnic Minority ◽

Ethnic Groups ◽

Psychotic Disorders ◽

Meta Analysis ◽

Psychotic Symptoms ◽

Migrant Status ◽

Increased Risk ◽

Black Populations

AbstractPsychotic symptoms (PS) are experienced by a substantial proportion of the general population. When not reaching a threshold of clinical relevance, these symptoms are defined as psychotic experiences (PEs) and may exist on a continuum with psychotic disorders. Unfavorable socio-environmental conditions, such as ethnic minority position (EMP) and migrant status (MS), may increase the risk of developing PS and PEs. We conducted an electronic systematic review and a meta-analysis assessing the role of EMP and MS for the development and persistence of PS in the general population. Sub-group analyses were performed investigating the influence of ethnic groups, host countries, age, types of PS, and scales. Twenty-four studies met our inclusion criteria. EMP was a relevant risk factor for reporting PS [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.22–1.70) and PEs (OR 1.36, 95% CI 1.16–1.60). The greatest risk was observed in people from the Maghreb and the Middle East ethnic groups in Europe (OR 3.30, 95% CI 2.09–5.21), in Hispanic in the USA (OR 1.98, 95% CI 1.43–2.73), and in the Black populations (OR 1.85, 95% CI 1.39–2.47). We found a significant association between MS and delusional symptoms (OR 1.47, 95% CI 1.33–1.62). We found no association between EMP and persistence of PEs.EMP was associated with increased risk of reporting PS and PEs, and the risk was higher in ethnic groups facing deprivation and discrimination. We found an association between MS and delusional symptoms. These results raise questions about the precise role of socio-environmental factors along the psychosis continuum.

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Substance use in psychiatric crisis: relationship to violence

Psychological Medicine ◽

10.1017/s0033291720003451 ◽

2020 ◽

pp. 1-7

Author(s):

Nicola J. Kalk ◽

John E. Robins ◽

Kezia R. Ross ◽

Megan Pritchard ◽

Michael T. Lynskey ◽

...

Keyword(s):

Substance Use ◽

Psychotic Disorders ◽

Healthcare Setting ◽

Psychotic Symptoms ◽

Emergency Setting ◽

Violent Behaviour ◽

Stimulant Use ◽

Healthcare Settings ◽

Increased Risk ◽

The Relationship

Abstract Background Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoid and stimulant use, and acute psychotic symptoms, in relation to violent behaviour in a British emergency healthcare setting. Methods We used electronic medical records from detentions of 1089 individuals under Section 136 of the UK Mental Health Act (1983 amended 2007), an emergency police power used to detain people for 24–36 h for psychiatric assessment. The relationship between recent cannabinoids and/or stimulant use, psychotic symptoms, and violent behaviour, was estimated using logistic regression. Findings There was evidence of recent alcohol or drug use in 64.5% of detentions. Violent incidents occurred in 12.6% of detentions. Psychotic symptoms increased the odds of violence by 4.0 [95% confidence intervals (CI) 2.2–7.4; p < 0.0001]. Cannabinoid use combined with psychotic symptoms increased the odds of violence further [odds ratios (OR) 7.1, 95% CI 3.7–13.6; p < 0.0001]. Recent use of cannabinoids with stimulants but without psychotic symptoms was also associated with increased odds of violence (OR 3.3, 95% CI 1.4–7.9; p < 0.0001). Interpretation In the emergency setting, patients who have recently used cannabinoids and exhibit psychotic symptoms are at higher risk of violent behaviour. Those who have used both stimulants and cannabinoids without psychotic symptoms may also be at increased risk. De-escalation protocols in emergency healthcare settings should account explicitly for substance use.

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