The Effectiveness of Cannabinoids in the Treatment of Posttraumatic Stress Disorder (PTSD): A Systematic Review.

Objectives: Posttraumatic stress disorder (PTSD) is a potentially debilitating mental health problem. There has been a recent surge of interest regarding the use of cannabinoids in the treatment of PTSD. We therefore sought to systematically review and assess the quality of the clinical evidence of the effectiveness of cannabinoids for the treatment of PTSD. Method: We included all studies published until December 2018 where a patient has had PTSD diagnosed and had been prescribed or were using a cannabinoid for the purpose of reducing PTSD symptoms. Our primary outcome measure was the reduction in PTSD symptoms using a validated instrument. In the absence of randomized controlled trials, we included the next best available levels of evidence including observational and retrospective studies and case reports. We assessed risk of bias and quality using validated tools appropriate for the study design. Results: We included 10 studies in this review, of which only one study was a pilot randomized, double-blind, placebo-controlled, crossover clinical trial. Every identified study had medium to high risk of bias and was of low quality. We found that cannabinoids may decrease PTSD symptomology, in particular sleep disturbances and nightmares. Conclusions: Most studies to date are small and of low quality, with significant limitations to the study designs precluding any clinical recommendations about its use in routine clinical practice. Evidence that cannabinoids may help reduce global PTSD symptoms, sleep disturbances, and nightmares indicates that future well-controlled, randomized, double-blind clinical trials are highly warranted.PROSPERO registration number: 121646.

Salience attribution and its relationship to cannabis-induced psychotic symptoms.

BACKGROUND: Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity. METHOD: We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant K i cer , was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography. RESULTS: There was no significant difference in aberrant salience between the groups [F 1,32 = 1.12, p = 0.30 (implicit); F 1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F 1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = -0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = -2.05, p = 0.04). CONCLUSIONS: Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.

The practical management of refractory schizophrenia--the Maudsley Treatment REview and Assessment Team service approach.

OBJECTIVE: To describe a practical approach to the community management of treatment-resistant schizophrenia (TRS). METHOD: A descriptive review of an approach to the assessment and management of patients with TRS, including the community titration of clozapine treatment, and a report of the management recommendations for the first one hundred patients assessed by the Treatment REview and Assessment Team (TREAT). RESULTS: The standardized model for the community assessment, management and titration of clozapine is described. To date, 137 patients have been referred to this service and 100 patients (72%) attended for assessment. Of these, 33 have been initiated on clozapine while fifteen have had clozapine recommended but have not wished to undertake clozapine treatment. Other management options recommended have included augmentation strategies and long-acting injectable antipsychotics. CONCLUSION: The service had increased the number of patients receiving community assessment and initiation of clozapine by five-fold relative to the rate prior to the establishment of the service. The large number of referrals and high attendance rate indicates that there is clinical demand for the model. Systematic evaluation is required to determine the clinical and cost-effectiveness of this model and its potential application to other clinical settings.

Age differences in the behavioural economics of cannabis use: Do adolescents and adults differ on demand for cannabis and discounting of future reward?

BACKGROUND: Adolescence is a period of psychological and neural development in which harms associated with cannabis use may be heightened. We hypothesised that adolescent who use cannabis (adolescentsWUC) would have steeper delay discounting (preference for immediate over future rewards) and greater demand (relative valuation) for cannabis than adults who use cannabis (adultsWUC). METHODS: This cross-sectional study, part of the 'CannTeen' project, compared adultsWUC (n = 71, 26-29 years old) and adolescentsWUC (n = 76, 16-17 years old), and gender- and age-matched adolescent (n = 63) and adult (n = 64) controls. AdolescentsWUC and adultsWUC used cannabis 1-7 days/week and were matched on cannabis use frequency (4 days/week). The Monetary Choice Questionnaire assessed delay discounting. A modified Marijuana Purchase Task (MPT) assessed cannabis demand in adolescentsWUC and adultsWUC. The MPT yielded five indices: intensity (amount of cannabis used at zero cost), Omax (total peak expenditure), Pmax (price at peak expenditure), breakpoint (cost at which cannabis demand is suppressed to zero) and elasticity (degree to which cannabis use decreases with increasing price). Analyses were adjusted for covariates of gender, socioeconomic status, other illicit drug use. RESULTS: Both adolescentsWUC and adultsWUC had steeper delay discounting than controls (F, (1,254)= 9.13, p = 0.003, ηp2= 0.04), with no significant age effect or interaction. AdolescentsWUC showed higher intensity (F, (1,138)= 9.76, p = 0.002, ηp2= 0.07) and lower elasticity (F, (1,138)= 15.25, p < 0.001, ηp2= 0.10) than adultsWUC. There were no significant differences in Pmax, Omax or breakpoint. CONCLUSION: Individuals who use cannabis prefer immediate rewards more than controls. AdolescentsWUC, compared to adultsWUC, may be in a high-risk category with diminished sensitivity to cannabis price increases and a greater consumption of cannabis when it is free.