History Of Cannabis Use Disorders Research Articles

Sex differences in the acute effects of oral THC: a randomized, placebo-controlled, crossover human laboratory study.

Recent reports have shown increased cannabis use among women, leading to growing concerns about cannabis use disorder (CUD). While there is preclinical evidence suggesting biological sex influences cannabinoid effects, human research remains scant. We investigated sex differences in the acute response to oral tetrahydrocannabinol (THC) in humans. 56 healthy men and women with prior exposure to cannabis but no history of CUD participated in a randomized, placebo-controlled, human laboratory study where they received a single 10mg dose of oral THC (dronabinol). Subjective psychoactive effects were assessed by the visual analog scale of "high", psychotomimetic effects by the Clinician-Administered Dissociative Symptoms Scale and Psychotomimetic States Inventory, verbal learning and memory by Rey Auditory Verbal Learning Test (RAVLT), and physiological effects by heart rate. Outcomes were regularly measured on the test day, except for the RAVLT, which was assessed once. Peak differences from baseline were analyzed using a nonparametric method for repeated measures. Oral THC (10mg) demonstrated significant dose-related effects in psychotomimetic and physiological domains, but not in RAVLT outcomes. A notable interaction between THC dose and sex emerged concerning the subjective "high" scores, with women reporting heightened sensations (p = 0.05). No other significant effects of sex and THC dose interaction were observed. Oral THC (10mg) yields similar acute psychotomimetic and physiological effects across sexes, but women may experience a pronounced subjective psychoactive effect. Further research is needed to identify individual vulnerabilities and facilitate tailored interventions addressing CUD. GOV REGISTRATION: https://clinicaltrials.gov/study/NCT02781519?term=Ranganathan&intr=THC&rank=3 .

Cannabinoid syndrome in cannabis dependence: a case report

IntroductionA 36-year-old man with a history of cannabis use disorder since age 16, consuming 8-10 units/day, experienced irritability and tremors upon reducing consumption. His psychiatric issues emerged in 2020, marked by anxiety, abdominal pain, and severe vomiting, leading to a dyspepsia diagnosis. Subsequently, he received psychiatric care at CAS Hospitalet, diagnosed with severe cannabis use disorder. No prior inpatient admissions occurred.Objectives Our project aims to show a case report and summarize the available evidence on cannabinoid hyperemesis syndrome (CHS).MethodsIn May 2023, he voluntarily sought admission to Barcelona’s “Hospital Sant Pau,” aiming for cannabis detox and treatment of cannabinoid hyperemesis. He’d endured years of intense abdominal pain, nausea, and vomiting, worsening over the last two years, with uncontrollable vomiting hindering daily life. Admission saw reduced cannabis use to 3-4 units/day. Inpatient care revealed anticipatory anxiety, rumination, and somatic anxiety, accompanied by distal tremors and internal restlessness due to abdominal discomfort, partially alleviated by 5-10 mg of diazepam.ResultsTreatment included domperidone 10mg/8h, haloperidol drops (5-10 drops/8h), capsaicin ointment, hot showers, and cryotherapy, resulting in gradual relief from abdominal pain. Moderate cravings for tobacco and cannabis led to acetylcysteine 600mg/12h and gabapentin up to 1200mg/8h. Gastric discomfort with SSRIs led to vortioxetine 10 mg/day, well-tolerated with a positive response. Consultation with the GI department confirmed the treatment’s efficacy, emphasizing cannabis abstinence. Upon discharge, cannabinoid hyperemesis symptoms markedly improved, and the patient was referred to “Hospital de Dia.”Conclusions CHS is a cyclic vomiting syndrome, preceded by daily to weekly chronic longstanding use of cannabis that can be difficult to diagnose and treat(1,3,4). It is unique in presentation, because of the cannabis’s biphasic effect as anti-emetic at low doses and pro-emetic at higher doses, and the association with pathological hot water bathing (2). The major characteristics are as follows: history of regular cannabis for any duration of time (100%), cyclic nausea and vomiting (100%), resolution of symptoms after stopping cannabis (96.8%), compulsive hot baths with symptom relief (92.3%), male predominance (72.9%), abdominal pain (85.1%), and at least weekly cannabis use (97.4%)(1). Treatments such as topical capsaicin, haloperidol, benzodiazepines, and propranolol have shown symptom relief (3) whereas opioids should be avoided (4). Cannabis cessation appears to be the best treatment (1,3).

4 Methamphetamine, cannabis, HIV, and their combined effects on neurocognition

Objective:Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.Participants and Methods:HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.Results:Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.Conclusions:In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.

Cannabis use may attenuate neurocognitive performance deficits resulting from methamphetamine use disorder.

Methamphetamine and cannabis are two widely used, and frequently co-used, substances with possibly opposing effects on the central nervous system. Evidence of neurocognitive deficits related to use is robust for methamphetamine and mixed for cannabis. Findings regarding their combined use are inconclusive. We aimed to compare neurocognitive performance in people with lifetime cannabis or methamphetamine use disorder diagnoses, or both, relative to people without substance use disorders. 423 (71.9% male, aged 44.6 ± 14.2 years) participants, stratified by presence or absence of lifetime methamphetamine (M-/M+) and/or cannabis (C-/C+) DSM-IV abuse/dependence, completed a comprehensive neuropsychological, substance use, and psychiatric assessment. Neurocognitive domain T-scores and impairment rates were examined using multiple linear and binomial regression, respectively, controlling for covariates that may impact cognition. Globally, M+C+ performed worse than M-C- but better than M+C-. M+C+ outperformed M+C- on measures of verbal fluency, information processing speed, learning, memory, and working memory. M-C+ did not display lower performance than M-C- globally or on any domain measures, and M-C+ even performed better than M-C- on measures of learning, memory, and working memory. Our findings are consistent with prior work showing that methamphetamine use confers risk for worse neurocognitive outcomes, and that cannabis use does not appear to exacerbate and may even reduce this risk. People with a history of cannabis use disorders performed similarly to our nonsubstance using comparison group and outperformed them in some domains. These findings warrant further investigation as to whether cannabis use may ameliorate methamphetamine neurotoxicity.

Twelve-year neurocognitive decline in HIV is associated with comorbidities, not age: a CHARTER study.

Modern antiretroviral therapy (ART) has increased longevity of people with HIV and shifted the age distribution of the HIV pandemic upward toward that of the general population. This positive development has also led to concerns about premature and/or accelerated neurocognitive and physical ageing due to the combined effects of chronic HIV, accumulating comorbidities, adverse effects or possible toxicities of ART and biological ageing. Here we present results of comprehensive assessments over 12 years of 402 people with HIV in the CNS HIV ART Effects Research (CHARTER) programme, who at follow-up were composed of younger (<60 years) and older (≥60 years) subgroups. Over the 12 years, ART use and viral suppression increased in both subgroups as did systemic and psychiatric comorbidities; participants in both subgroups also evidenced neurocognitive decline beyond what is expected in typical ageing. Contrary to expectations, all these adverse effects were comparable in the younger and older CHARTER subgroups, and unrelated to chronological age. Neurocognitive decline was unrelated to HIV disease or treatment characteristics but was significantly predicted by the presence of comorbid conditions, specifically diabetes, hypertension, chronic pulmonary disease, frailty, neuropathic pain, depression and lifetime history of cannabis use disorder. These results are not consistent with premature or accelerated neurocognitive ageing due to HIV itself but suggest important indirect effects of multiple, potentially treatable comorbidities that are more common among people with HIV than in the general population. Good medical management of HIV disease did not prevent these adverse outcomes, and increased attention to a range of comorbid conditions in people with HIV may be warranted in their care.

Associations of Current and Remitted Cannabis Use Disorder With Health-related Quality of Life and Employment Among US Adults.

The associations of current and remitted cannabis use disorder (CUD) with health-related quality of life (HRQOL) and employment have not been studied, and we aim to address these gaps. The 2012-2013 National Epidemiological Survey on Alcohol and Related Conditions III (NESARC III) surveyed a nationally representative sample of non-institutionalized civilian US adults (≥18 years) (n = 36,309 unweighted). Using DSM-5 criteria, adults with current CUD were compared with those with CUD in remission and no history of CUD on standard measures of the mental and physical component scores of HRQOL and of quality-adjusted life years (QALYs) along with employment in the past 12 months. Multivariable-adjusted regression analyses were used to adjust for and examine the role of covariates. Overall, 2.5% of the study sample, representing 6.0 million adults nationwide, met criteria for current CUD, and 3.7%, representing 8.8 million adults, met the criteria for CUD in remission. Adults with current or past CUD had lower mental HRQOL and QALYs, as compared to adults who never had CUD. However, these differences were no longer significant when adjusted for behavioral co-morbidities and personal histories. Current CUD was associated with lower odds of being employed (Adjusted odds ratio AOR = 0.76; 95% confidence intervals [CI], 0.60-0.96), but CUD in remission with a greater likelihood of employment (Adjusted odds ratio = 1.53; 95% CI, 1.23-1.91), both as compared to those never experiencing CUD. Both current CUD and past CUD are adversely associated with HRQOL and current CUD with not being employed; Since CUD associations are not independent of comorbidities, treatment must take a wide-ranging approach.

Cohort Study of Cannabis Use History and Perinatal Cigarette Use Among Overweight and Obese Women.

In non-pregnant populations, cannabis use and cannabis use disorder (CUD) have been linked to tobacco use and less successful quit attempts. We compared perinatal cigarette use in women across 3 groups: never used cannabis (No CU group); used cannabis but did not meet CUD criteria (CU group); history of CUD (CUD group). Interviews with 257 pregnant women with overweight/obesity (M age = 28years; 52% white) were conducted for a study of eating behavior in Western Pennsylvania from 2012-2016. Tobacco use was assessed early in pregnancy (< 20weeks gestation), late in pregnancy (34-38weeks gestation) and 6months postpartum. CUD was measured with the Structured Clinical Interview for DSM-IV (SCID). Data relevant to the proposed analyses were available for 252 women. Generalized mixed effect models were used to predict perinatal cigarette use based on cannabis use group, time and their interaction, adjusting for age, race, education, income, parity, and mood/anxiety disorder. Forty-eight percent of participants reported prior cannabis use and 15% were diagnosed with lifetime CUD. History of cannabis use predicted cigarette smoking in early pregnancy (OR 11.12, CI 3.27-37.85), late pregnancy (OR 6.55, CI 1.70-25.27), and 6months postpartum (OR 7.57, CI 2.72-21.07), regardless of CUD. A history of CUD did not appear to confer additional risk for perinatal cigarette use. Given increasing rates of cannabis use among pregnant women, these results highlight the importance of addressing history of cannabis use in conjunction with tobacco use to improve smoking cessation efforts.

Cannabis use disorder among atrial fibrillation admissions, 2008-2018.

Despite changes inthe legality of cannabis use and the increasing prevalence of cannabis use disorder (CUD), there is little data investigating the association between CUD and inpatient atrial fibrillation (AF) hospitalizations. Using the National Inpatient Sample, we identified Atrial Fibrillation (AF) hospitalizations with and without a codiagnosis of CUD using International Classification of Diseases diagnosis codes and compared demographics, socioeconomics, comorbidities, outcomes, and trends between cohorts. Between 2008 and 2018, we identified 5,155,789 admissions for AF of which 31,768 (0.6%) had a codiagnosis of CUD. The proportion of admissions with a history of CUD increased from 0.3% in 2008 to 1.0% in 2018 (p<.001). Hospital discharges of patients with CUD were significantly younger (53 vs. 72years, p<.001), had a higher proportion of black race (CUD: 26.6% vs. 8.0%, p<.001), and had a higher proportion of income in the lowest income quartile than without a codiagnosis of CUD (CUD: 40.5% vs. 26.2%, p<.001). CUD is increasingly prevalent among AF hospitalizations, particularly among young patients. Codiagnosis of CUD in AF hospitalizations is also more common in underserved patients. As a result, it is important for future research to examine and understand the impact of CUD on this population, particularly in the light of changing legislation surrounding the legality of cannabis.

Cannabis use disorder and the future risk of cardiovascular disease in parous women: a longitudinal cohort study

BackgroundCannabis use is increasing in women of reproductive age, but whether cannabis use disorders increase the long-term risk of cardiovascular disease in this population is not known. Cannabis may cause tachycardia, hypertension, cerebral vasoconstriction, and other adverse cardiovascular effects and has been associated with acute myocardial infarction and stroke. Data on the long-term effects of cannabis on the cardiovascular system are more limited. We assessed the relationship between cannabis use disorders early in life and the future risk of cardiovascular disease in women.MethodsWe analyzed a longitudinal cohort of 1,247,035 pregnant women in Quebec, Canada, between 1989 and 2019. The main exposure was current or past history of cannabis use disorders at cohort entry. The main outcome measure included future hospital admission for any cardiovascular disorder during 18,998,986 person years of follow-up. We used Cox proportional hazards regression models adjusted for patient characteristics to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of cannabis use disorder with the later risk of cardiovascular hospitalization.ResultsWomen with cannabis use disorders had a higher incidence of cardiovascular hospitalization than unexposed women (58.4 vs. 33.6 per 10,000 person years). Cannabis use disorder was associated with 1.48 times the risk of cardiovascular hospitalization (95% CI 1.27–1.72), compared with no cannabis use disorder. The association was greater for cannabis with concomitant use of other substances (HR 1.84, 95% CI 1.53–2.21) than for cannabis alone (HR 1.30, 95% CI 0.99–1.72). Cannabis use disorder was strongly associated with hemorrhagic stroke, even with adjustment for other substance use (HR 2.08, CI 1.07–4.05).ConclusionsCannabis use disorders may increase the long-term risk of cardiovascular disease in women, particularly hemorrhagic stroke. However, some of the excess risk may be due to concomitant use of other substances.

WHIPPIT - WHIPPED THE LUNG

SESSION TITLE: Medical Student/Resident Disorders of the Pleura Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pneumothorax (PTX) can be a complication of invasive mechanical ventilation due to abrupt changes in pressure within the thoracic cavity. It can also occur due to sudden change in the intra-thoracic pressure as a complication of inhaled illicit substances such as cocaine and 3,4-Methylenedioxymethamphetamine (MDMA) (1,2). The recreational use of inhaled nitric oxide continues to rise, with prolonged inhalation leading to neurological complications (3). Here, we present a case of a PTX after inhalation of pressurized nitric oxide in a patient without any prior lung disease, a complication not previously reported. CASE PRESENTATION: A 25-year-old man with history of cannabis use disorder presented with sudden onset left sided chest pain and dyspnea that started after inhaling two canisters of Whippits (pressurized whipped cream chargers filled with nitric oxide). He was tachycardic and tachypneic upon presentation and was noted to have absent breath sounds over left hemi-thorax. Initial laboratory investigations including a complete blood count and comprehensive metabolic panel were unremarkable. Chest X-ray (CXR) revealed a large left PTX with complete collapse of the left lung. A chest tube was inserted on the left hemithorax with resolution of his symptoms and the PTX on imaging. A computed tomography of the chest showed no underlying lung disease. The patient was discharged with recommendations to abstain from inhaled nitric oxide use. DISCUSSION: PTX due to nitric oxide inhalation is uncommon, and to our knowledge no cases have been previously reported. However, PTX and pneumomediastinum from Valsalva maneuvers after use of inhaled drugs have been reported and have been associated with marijuana use (4,5,6). Although, there is no direct role of marijuana in the development of emphysema, high burden of inflammatory cells leading to lung injury and subsequent emphysema has been described (5). In our patient, who had no prior underlying lung disease, the development of PTX most likely resulted from sudden and rapid change in intra-alveolar pressure secondary to forced lung expansion from a Valsalva maneuver after inhalation of pressurized nitric oxide. CONCLUSIONS: Nitric oxide induced PTX has not been previously reported in the literature. In our patient, PTX in the absence of underlying primary lung disease can be explained by barotrauma from rapid inhalation of nitric oxide via Whippits. Further studies are warranted to evaluate the risk factors and incidence of PTX with pressurized nitric oxide inhalation. Reference #1: Ioannidis G, Lazaridis G, Baka S, et al. Barotrauma and pneumothorax. J Thorac Dis. 2015;7(Suppl 1):S38–S43. doi:10.3978/j.issn.2072-1439.2015.01.31 Reference #2: 2) Jaensch S, Hwang S, Shih-Wei-Kuo T. Spontaneous Pneumomediastinum and Subcutaneous Emphysema following Cocaine Inhalation and Ecstasy Ingestion. Case Reports in Otolaryngology. 2019; doi: 10.1155/2019/6972731 Reference #3: 3) Thompson AG, Leite MI, Lunn MP, Bennett DL. Whippits, nitrous oxide and the dangers of legal highs. Pract Neurol. 2015;15(3):207–209. doi:10.1136/practneurol-2014-001071 4) Hauben M, Hung EY. Pneumothorax as an adverse drug event: an exploratory aggregate analysis of the US FDA AERS database including a confounding by indication analysis inspired by Cornfield's condition. Int J Med Sci. 2013;10(8):965–973. Published 2013 Jun 13. doi:10.7150/ijms.5377 5) Mishra R, Patel R, Khaja M. Cannabis-induced bullous lung disease leading to pneumothorax: Case report and literature review. Medicine (Baltimore). 2017;96(19):e6917. doi:10.1097/MD.0000000000006917 6) Miller, W. Eugene, et al. “Pneumomediastinum Resulting from Performing Valsalva Maneuvers during Marihuana Smoking.” Chest, vol. 62, no. 2, 1972, pp. 233–234., doi:10.1378/chest.62.2.233. DISCLOSURES: No relevant relationships by Moeezullah Beg, source=Web Response No relevant relationships by Tasnim Islam, source=Web Response Consultant relationship with GSK Please note: $5001 - $20000 Added 04/23/2020 by Diego Maselli Caceres, source=Web Response, value=Consulting fee Consultant relationship with AstraZeneca Please note: $5001 - $20000 Added 04/23/2020 by Diego Maselli Caceres, source=Web Response, value=Consulting fee Consultant relationship with Sanofi/Regeneron Please note: $5001 - $20000 Added 04/23/2020 by Diego Maselli Caceres, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Sunovion Please note: $5001 - $20000 Added 04/23/2020 by Diego Maselli Caceres, source=Web Response, value=Honoraria Consultant relationship with Novartis Please note: $1001 - $5000 Added 04/23/2020 by Diego Maselli Caceres, source=Web Response, value=Consulting fee

Interaction of Cannabis Use Disorder and Striatal Connectivity in Antipsychotic Treatment Response.

Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between a history of cannabis use disorder (CUD) and a striatal connectivity index (SCI), a previously developed neural biomarker for AP treatment response in SSD. Patients were part of a 12-week randomized, double-blind controlled treatment study of AP drugs. A sample of 48 first-episode SSD patients with no more than 2 weeks of lifetime exposure to AP medications, underwent a resting-state fMRI scan pretreatment. Treatment response was defined a priori as a binary (response/nonresponse) variable, and a SCI was calculated in each patient. We examined whether there was an interaction between lifetime CUD history and the SCI in relation to treatment response. We found that CUD history moderated the relationship between SCI and treatment response, such that it had little predictive value in SSD patients with a CUD history. In sum, our findings highlight that biomarker development can be critically impacted by patient behaviors that influence neurobiology, such as a history of CUD.

Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis Use Disorders.

In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs). Bipolar depressed participants were enrolled in a randomized placebo-controlled clinical trial to evaluate the efficacy of add-on pregnenolone for depression and before receiving pregnenolone or placebo. Baseline serum levels of neurosteroids (pregnenolone, allopregnanolone, pregnanolone, and androsterone) were analyzed in 53 participants with highly sensitive and specific gas chromatography/mass spectrometry. Current, active substance use disorders, or a positive baseline urine drug screen, were exclusionary. Participants were classified by past cannabis abuse or dependence diagnosis using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Data were analyzed by independent t tests for separate neurosteroids. Participants with a history of CUD had higher serum pregnanolone, lower allopregnanolone, a higher pregnanolone to allopregnanolone ratio, and a lower pregnenolone to pregnanolone ratio compared with those without a history of cannabis use. Similar findings were not observed based on a history of other substance use disorders with the exception of lower allopregnanolone in those with opioid use disorders. Notably, the majority of those with an opioid use disorder also had a CUD (75%). These findings potentially suggest either enduring changes in neurosteroids in people with past CUDs or represent a vulnerability marker for a CUD.

Cannabis-related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects.

Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ-CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON-CUD were associated with poorer EM performance, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis.

Cognitive and clinical outcomes associated with cannabis use in patients with bipolar I disorder

Studies investigating the impact of cannabis use on bipolar clinical characteristics and neurocognition are limited. The objective of the present study was to compare clinical and neurocognitive measures in individuals with bipolar disorder with a history of cannabis use disorder (CUD) versus those without a history of CUD. We conducted a retrospective analysis of a large cohort (N=200) of bipolar I subjects, either with (CUD+; N=50) or without (CUD−; N=150) a history of CUD. We compared the groups on clinical and demographic variables, as well as on performance on neurocognitive tests. Patient groups did not differ regarding age, age of onset or global assessment of functioning. Compared to the CUD− group, the CUD+ group had a higher proportion of men and a higher proportion of patients with a history of psychosis. CUD+ subjects demonstrated significantly better performance on measures of attention, processing speed, and working memory. The history of CUD is associated with history of psychosis, suggestive of poorer clinical prognosis. Interestingly, bipolar patients with history of CUD had better neurocognitive performance as compared to patients with no history of CUD.

Olanzapine vs. risperidone in patients with first-episode schizophrenia and a lifetime history of cannabis use disorders: 16-week clinical and substance use outcomes

The purpose of this study is to compare the efficacy of olanzapine and risperidone for the acute treatment of first-episode schizophrenia patients with cannabis use disorders. This secondary analysis of a previously published study included 49 first-episode patients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder and a co-occurring lifetime diagnosis of cannabis use disorders randomly assigned to treatment with either olanzapine (n=28) or risperidone (n=21) for 16weeks. The olanzapine group did not differ significantly from the risperidone group for initial response rates of positive symptoms, and rates of cannabis use or alcohol use during the study. Positive symptoms and the Scale for Assessment of Negative Symptoms (SANS) global asociality-anhedonia scores improved over time but did not differ between study medications. In both groups, cannabis use during the study was higher in patients who used cannabis within three months of the admission. Thus, our results suggest that olanzapine and risperidone had a similar initial efficacy on psychotic symptoms and substance use in first-episode patients with co-occurring cannabis use disorders. If clinicians are choosing between olanzapine versus risperidone treatment for this population, their decision should be based upon factors other than symptom response and short-term substance misuse.

Cannabis use disorders in schizophrenia: Effects on cognition and symptoms

ObjectiveDespite the controversy surrounding the possible causal link between cannabis use and the onset of schizophrenia (SZ), data seeking to elucidate the effect of cannabis use disorders (CUDs) on the clinical presentation of SZ have produced mixed results. Although several studies have suggested that CUD in patients with SZ may be associated with variation in cognitive function, clinical presentation and course of illness, the effects have been inconsistent. MethodsWe retrospectively ascertained a large cohort (N=455) of SZ patients with either no history of a CUD (CUD−; N=280) or a history of CUD (CUD+; N=175). The groups were initially compared on key demographic variables including sex, race, age, age at onset of SZ, parental socioeconomic status, premorbid IQ, education level and global assessment of functioning. Covarying for any observed differences in demographic variables, we then compared groups on lifetime measures of psychotic symptoms as well as a brief battery of neurocognitive tests. ResultsCompared to the CUD− group the CUD+ group demonstrated significantly better performance on measures of processing speed (Trail Making Tests A and B), verbal fluency (animal naming) and verbal learning and memory (California Verbal Learning Test). Moreover, the CUD+ group had better GAF scores than the CUD group. ConclusionsCollectively, these findings suggest that SZ patients with comorbid CUD may represent a higher functioning subgroup of SZ. Future prospective studies are needed to elucidate the nature of this relationship.

Are cannabis use disorders associated with an earlier age at onset of psychosis? A study in first episode schizophrenia

IntroductionThe purpose of this study is to determine if an earlier age at onset of positive symptoms in schizophrenia is associated with cannabis use disorders (CUD). Methods49 first-episode schizophrenia subjects with CUD were compared to 51 first-episode schizophrenia subjects with no substance use disorders for demographic and clinical variables. A multivariate logistic regression was performed to determine the joint relationship between variables significantly associated with CUD on univariate testing and ascertain if these variables independently predict CUD. Significance level was set at p<0.05. Results74% of CUD subjects had the onset of CUD before the onset of positive symptoms. Compared to non-substance abusing subjects, CUD subjects were predominantly male, younger at study entry, had an earlier age at onset of positive symptoms, less educational attainment, a lower self-socioeconomic status, better premorbid childhood social adjustment, a trend for poorer premorbid childhood academic adjustment, less motor abnormalities but more severe hallucinations and delusions. In the multivariate analysis, only male gender, worse socio-economic status, better premorbid childhood social adjustment, and more severe positive symptoms at study entry were associated with a lifetime history of CUD. DiscussionAlthough cannabis use precedes the onset of illness in most patients, there was no significant association between onset of illness and CUD that was not accounted for by demographic and clinical variables. Previous studies implicating CUD in the onset of schizophrenia may need to more comprehensively assess the relationship between CUD and schizophrenia, and take into account additional variables that we found associated with CUD.

The familial aggregation of cannabis use disorders

The aim of this paper is to examine the familial aggregation of cannabis use disorders and other psychiatric conditions among first-degree relatives and spouses of probands with a cannabis use disorder. Controlled family study methods. Out-patient psychiatric clinics and the local community (same geographic area). Two hundred and sixty-two probands with a life-time history of cannabis use disorder, alcohol dependence, anxiety disorders or no history of any disorder, and their first-degree relatives and spouses. Cannabis use disorders and other DSM-III-R disorders in the relatives and spouses using the Schedule for Affective Disorders and Schizophrenia. Results reveal an elevated risk of life-time history of cannabis use disorders among siblings [odds ratio (OR: 3.6), adult offspring (OR): 6.9], and spouses (OR: 4.4) of probands with cannabis use disorders. There is a latent familial factor underlying cannabis use disorders that was shared partially with alcohol abuse/dependence. Comorbid mood and anxiety disorders aggregated independently from cannabis use disorders in families. Equal elevation in the magnitude of the association among the first-degree adult relatives and spouses of probands with a cannabis use disorder suggests the probable contribution of both environmental and genetic factors. These findings support a family-based approach to drug abuse intervention and the importance of future research concerning environmental mediators of familial transmission of drug abuse.