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Pharmacological treatments targeting the neuroendocrine stress response may hold special promise in secondary prevention of posttraumatic stress disorder (PTSD). However, findings from clinical trials have been inconsistent and the efficacy of specific drugs, their temporal window of efficacy, effective doses and the characteristics of likely treatment responders remain unclear.
Using an experimental human model of distressing involuntary memory formation, we compare the effects of two drugs that have theoretical or empirical support as secondary preventive agents in PTSD. Eighty-eight healthy women (average age: 23.5 years) received oral propranolol (80 mg), hydrocortisone (30 mg), or matched placebo immediately after viewing a ‘trauma film’. They then completed daily, time-stamped intrusion diaries for 1 week, at the end of which, voluntary memory was tested.
While neither drug affected voluntary memory for the trauma narrative, propranolol treatment was associated with 42% fewer, and hydrocortisone with 55% fewer intrusions across the week, relative to placebo. Additionally, propranolol reduced general trauma-like symptoms, and post-drug cortisol levels were negatively correlated with intrusion frequency in the hydrocortisone group.
Overall, this study shows substantial reductions in intrusive memories and preserved voluntary narrative-declarative memory following either propranolol or hydrocortisone in an experimental model of psychological trauma. As such, despite some inconsistencies in clinical trials, our findings support continued investigation of propranolol and hydrocortisone as secondary preventive agents for re-experiencing symptoms of PTSD. The findings also suggest that it is critical for future research to identify the conditions governing the preventive efficacy of these drugs in PTSD.
Changes in cannabis regulation globally make it increasingly important to determine what predicts an individual's risk of experiencing adverse drug effects. Relevant studies have used diverse self-report measures of cannabis use, and few include multiple biological measures. Here we aimed to determine which biological and self-report measures of cannabis use predict cannabis dependency and acute psychotic-like symptoms.
In a naturalistic study, 410 young cannabis users were assessed once when intoxicated with their own cannabis and once when drug-free in counterbalanced order. Biological measures of cannabinoids [(Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN) and their metabolites)] were derived from three samples: each participant's own cannabis (THC, CBD), a sample of their hair (THC, THC-OH, THC-COOH, CBN, CBD) and their urine (THC-COOH/creatinine). Comprehensive self-report measures were also obtained. Self-reported and clinician-rated assessments were taken for cannabis dependency [Severity of Dependence Scale (SDS), DSM-IV-TR] and acute psychotic-like symptoms [Psychotomimetic State Inventory (PSI) and Brief Psychiatric Rating Scale (BPRS)].
Cannabis dependency was positively associated with days per month of cannabis use on both measures, and with urinary THC-COOH/creatinine for the SDS. Acute psychotic-like symptoms were positively associated with age of first cannabis use and negatively with urinary THC-COOH/creatinine; no predictors emerged for BPRS.
Levels of THC exposure are positively associated with both cannabis dependency and tolerance to the acute psychotic-like effects of cannabis. Combining urinary and self-report assessments (use frequency; age first used) enhances the measurement of cannabis use and its association with adverse outcomes.
The number of people entering specialist drug treatment for cannabis problems has increased considerably in recent years. The reasons for this are unclear, but rising cannabis potency could be a contributing factor.
Cannabis potency data were obtained from an ongoing monitoring programme in the Netherlands. We analysed concentrations of δ-9-tetrahydrocannabinol (THC) from the most popular variety of domestic herbal cannabis sold in each retail outlet (2000–2015). Mixed effects linear regression models examined time-dependent associations between THC and first-time cannabis admissions to specialist drug treatment. Candidate time lags were 0–10 years, based on normative European drug treatment data.
THC increased from a mean (95% CI) of 8.62 (7.97–9.27) to 20.38 (19.09–21.67) from 2000 to 2004 and then decreased to 15.31 (14.24–16.38) in 2015. First-time cannabis admissions (per 100 000 inhabitants) rose from 7.08 to 26.36 from 2000 to 2010, and then decreased to 19.82 in 2015. THC was positively associated with treatment entry at lags of 0–9 years, with the strongest association at 5 years, b = 0.370 (0.317–0.424), p < 0.0001. After adjusting for age, sex and non-cannabis drug treatment admissions, these positive associations were attenuated but remained statistically significant at lags of 5–7 years and were again strongest at 5 years, b = 0.082 (0.052–0.111), p < 0.0001.
In this 16-year observational study, we found positive time-dependent associations between changes in cannabis potency and first-time cannabis admissions to drug treatment. These associations are biologically plausible, but their strength after adjustment suggests that other factors are also important.
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