The Impact of Cannabis Use on Clinical Outcomes in Recent Onset Psychosis

Background: There are inconsistencies in findings as to whether cannabis use has a negative impact on clinical outcomes for people with established psychosis. Effects may be more evident on patients with recent onset psychosis. Aim: To investigate the relationship between cannabis use and clinical outcome, including whether change in cannabis use affects psychotic symptoms, affective symptoms, functioning and psychotic relapse in a sample of people in early psychosis with comorbid cannabis abuse or dependence. Methods: One hundred and ten participants were examined prospectively with repeated measures of substance use antecedent to psychopathology at baseline, 4.5, 9, and 18 months. We used random intercept models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes. Results: There was no evidence of a specific association between cannabis use and positive symptoms, or negative symptoms, relapse or hospital admissions. However, a greater dose of cannabis was associated with subsequent higher depression and anxiety. Change in the amount of cannabis used was associated with statistically significant corresponding change in anxiety scores, but not depression. Additionally, reductions in cannabis exposure were related to improved patient functioning. Conclusions: Reducing cannabis may be directly associated with improvements in anxiety and functioning, but not other specific symptoms.Key words: psychosis, cannabis, substance use, dual diagnosis     

Daily Use,Especially of High-Potency Cannabis,Drives the Earlier Onset of Psychosis in Cannabis Users

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11–1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.Key words: psychotic disorders, age of onset, gender, cannabis, survival plots, drug use, high-potency cannabis     

Sex Differences in Age at Onset and Presentation of Trichotillomania and Trichobezoar: A 120-Year Systematic Review of Cases

Trichotillomania (hair-pulling disorder) has high female preponderance. It has been suggested that onset in early childhood represents a distinct developmental subtype that is characterized by higher prevalence of males compared to later onset cases. However, the empirical literature is scarce. We conducted a systematic review of case reports to examine the distribution of age at onset/presentation in males and females with trichotillomania or trichobezoar (a mass of hair in the gastrointestinal tract resulting from ingesting hair). We identified 1065 individuals with trichotillomania and 1248 with trichobezoar. In both samples, males, compared to females, had earlier age at presentation and greater proportion of cases in early childhood. These sex differences remained after potential confounding variables were accounted for. The results showed similar sex differences for age at onset, which was reported in 734 and 337 of the trichotillomania and trichobezoar cases, respectively. The findings may reflect neurodevelopmental underpinnings in early childhood trichotillomania.

     

Psychopathology in Epilepsy: Relationship of Seizure Type to Age at Onset

Study of patients with temporal lobe epilepsy and generalized epilepsy revealed no overall seizure type differences, nor overall age-at-onset effects, on MMPI measures of psychopathology. However, statistically significant interactions between seizure type and age at onset were obtained on several MMPI measures, and subsequent analyses revealed that patients with adolescent-onset temporal lobe epilepsy are at higher risk of developing psychological dysfunctions.     

3-Year Follow-up of Lower Risk Cannabis Use Patterns: Evidence from a Longitudinal Survey

Objectives:Following recommendations from the Lower Risk Cannabis Use Guidelines, we evaluated how lower risk cannabis use (late initiation and low use frequency) was associated with the risk of developing cannabis abuse/dependence over a 3-year follow-up period compared to 12-month abstinence (controls) or higher risk cannabis use (early initiation and higher use frequency). We also explored the effect of cannabis quantity.Methods:Data were obtained from the U.S. nationally representative survey, National Epidemiologic Survey on Alcohol and Related Conditions wave I (2001 to 2002) and wave II (2004 to 2005), which included 31,464 respondents with no lifetime history of cannabis abuse/dependence at the first interview. We applied multiple logistic regression and propensity score matching analyses to examine the association between different use patterns at wave I and cannabis abuse/dependence at wave II, adjusting for covariates. Lower risk cannabis use and the transition to higher use frequency were also assessed.Results:For propensity score analysis, lower risk cannabis use at wave I was associated with higher risk of cannabis use/dependence at wave II compared to controls (odds ratio [OR]: 4.27; 95% confidence interval [95% CI], 1.57 to 11.61); however, there was no association with use frequency increase (OR: 2.52; 95% CI, 0.88 to 7.17). Higher risk use had a greater risk of cannabis use/dependence than controls (OR: 6.27; 95% CI, 2.56 to 15.38) and lower risk use (OR: 2.69; 95% CI, 1.12 to 6.47). Logistic regression analyses showed similar results, except that lower risk use was significantly associated with use frequency increase (OR: 2.49; 95% CI, 1.22 to 5.08). For the lower risk use group, 1 to 3 joints/day of use was significantly associated with cannabis abuse/dependence.Conclusions:We found that following recommended use patterns can significantly lower one’s risk of cannabis abuse/dependence. However, risk of cannabis abuse/dependence is still 4 times higher than staying abstinent. Updated recommendations on safe cannabis exposure levels are needed to guide cannabis use in the general population after cannabis legalization.     

Age at initiation of amphetamine use and age at onset of psychosis: The Australian Survey of High Impact Psychosis

Individuals with a psychotic disorder who had a premorbid history of amphetamine use (n = 382) were analyzed in groups according to age of initiation to amphetamine (AIA) and mean number of years of duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in age at onset of psychotic illness (AOI) and DPEA. Although a temporal direct relationship between AIA and AOI was detected (mean duration 5.3 years), our findings suggested this association was spurious and better explained by a later initiation to amphetamine than to cannabis (by 2–3 years).     

The Compassionate Utilitarian: Reconciling the Competing Moral Values Behind Efforts to Regulate Cannabis Use

Arguments about whether or not to legalize and regulate the sale, possession, and use of cannabis for recreation can be framed as ethical debates. Typically, for example, an argument based on the four principles of biomedical ethics might note that this policy debate pits individual autonomy rights against the harms associated with increasing social acceptance of using cannabis. But these debates tend to rapidly devolve to arguments about data; what exactly are the benefits and harms associated with legalization? This makes it seem that people on either side of the legalization debate are mostly concerned about tangible benefits and harms associated with legalization. Yet, I argue, the legalization debate is actually a variation of long-running debates about harm reduction strategies in public health, which are about deeper concerns that won’t be resolved with more data. An alternative strategy for more productive ethical discussion is proposed.     

Relationship of Age at Onset, Chronologic Age, and Adequacy of Preoperative Performance to Verbal Memory Change After Anterior Temporal Lobectomy

Summary We examined the relationship of age of onset of epilepsy, chronological age at time of operation, and adequacy of preoperative memory performance to pre- to postoperative verbal memory decline. Patients who underwent left (n = 50) or right (n = 51) anterior temporal lobectomy (ATL) were administered tests of verbal episodic (list learning, paragraph recall) and semantic memory (visual naming, vocabulary), both preoperatively and 6 months postoperatively. As a group, left ATL patients showed the classic selective decrease on measures of episodic but not semantic memory. However, examination of episodic memory outcome showed considerable individual variability. Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients. Adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in postoperative memory performance for both left and right ATL patients and for multiple types of memory indices. The clinical and theoretical implications are discussed.     

The Phenomenology and Neurobiology of Delusion Formation During Psychosis Onset: Jaspers,Truman Symptoms,and Aberrant Salience

Following the publication of Karl Jaspers’ General Psychopathology (1913), delusions have been characterized as being nonunderstandable in terms of the person’s biography, motivations, and historical-cultural context. According to Jaspers, this loss of understandability is due to an underlying neurobiological process, which has interrupted the normal development of the individual’s personality. Inheriting the 19th-century division between the natural- and human-historical sciences, Jaspers emphasizes the psychological understanding of mental disorders as narrative-based, holistic, and contextual. By doing so, he embraces cultural, ethnic, and individual differences and anticipates a person-centered medicine. However, he also affirms the value of explanatory neurobiological approaches, especially in the research and diagnosis of delusions. The phenomenological approach leads to neurobiological hypotheses, which can be tested experimentally. The present article addresses these issues by illustrating Jaspers’ fundamental contribution to current neurobiological research concerning the formation of delusions during early phases of psychosis. Specifically, we present delusional mood and Truman symptoms as core phenomenological features at the origin of psychosis onset, and we discuss their neurobiological substrate with the aberrant salience and dopamine dysregulation models. Jaspers and his successors’ phenomenological approach suggests that delusion is formed through loss of context in its experiential-perceptual origins. This is consistent with the more recent neurobiological models.Key words: psychosis, schizophrenia, delusion, phenomenology, at risk, prodromal     

Schizophrenia and the Environment: Within-Person Analyses May be Required to Yield Evidence of Unconfounded and Causal Association—The Example of Cannabis and Psychosis

Hypotheses about the link between cannabis use and psychosis apply to the within-person level but have been tested mostly at the between-person level. We used a within-person design, in which a person serves as his own control, thus removing the need to consider confounding by any fixed (genetic and nongenetic) characteristic to study the prospective association between cannabis use and the incidence of attenuated psychotic experiences, and vice versa, adjusted for time-varying confounders. We combined 2 general population cohorts (at baseline: Early Developmental Stages of Psychopathology Study, n = 1395; Netherlands Mental Health Survey and Incidence Study-2, n = 6603), which applied a similar methodology to study cannabis use and attenuated psychotic experiences with repeated interviews (T0, T1, T2, and T3) over a period of approximately 10 years. The Hausman test was significant for the adjusted models, indicating the validity of the fixed-effects model. In the adjusted fixed-effects model, prior cannabis use was associated with psychotic experiences (aOR = 7.03, 95% CI: 2.39, 20.69), whereas prior psychotic experiences were not associated with cannabis use (aOR = 0.59, 95% CI: 0.21, 1.71). Longitudinal studies applying random-effects models to study associations between risk factors and mental health outcomes, as well as reverse causality, may not yield precise estimates. Cannabis likely impacts causally on psychosis but not the other way round.