Cannabis use is associated with low plasma endocannabinoid Anandamide in individuals with psychosis.

BACKGROUND: Cannabis use suppresses the endocannabinoid system in healthy individuals. However, the association between cannabis use with the endocannabinoid system is understudied in individuals with psychosis despite the high rate of cannabis use in these individuals. METHODS: We enrolled 83 individuals who were admitted to an inpatient psychiatric unit with psychotic presentations, and measured their plasma levels of main endocannabinoids, Anandamide (AEA) and 2-Acylglycerol (2-AG), and endocannabinoid related compounds, Palmitoylethanolamine, and N-oleoylethanolamine. Cannabis use was assessed with urine toxicology and frequency of cannabis use was assessed using self-reported questionnaires. The Positive and Negative Syndrome Scale was used to assess the severity of psychotic symptoms. RESULTS: Overall, we had 38 individuals in cannabis positive group (CN+) and 45 individuals in cannabis negative group (CN-). Compared to CN-, CN+ group had lower plasma levels of AEA, which remained significant after controlling for age, gender, race/ethnicity, and use of other drugs. CONCLUSION: Cannabis use is associated with low plasma AEA levels in individuals with psychosis, which is in the same line with reported suppressive effects of cannabis on the endocannabinoid system in healthy individuals. Further studies are needed to investigate the clinical significance of this finding.

Cannabinoid use in psychotic patients impacts inflammatory levels and their association with psychosis severity.

Inflammatory abnormalities are well-documented in individuals with chronic psychotic disorders. Particular attention has focused on interleukin-6 (IL-6) and its correlation with psychotic symptom severity. Cannabis use is associated with an increased risk of psychosis and also has immunomodulating properties. It has been hypothesized that inflammatory disturbances are a common underlying pathology between cannabis use and psychosis. We measured inflammatory markers in individuals admitted to a psychiatric unit with acute psychosis who had toxicology positive for natural and/or synthetic cannabinoids (n = 59) compared to patients with negative cannabinoid toxicology (n = 60). Psychosis severity was assessed using the Positive and Negative Syndrome Scale (PANSS). While PANSS scores were similar between groups, cannabinoid-positive participants were more likely to receive pro re nata (PRN or as-needed) medications for agitation in the psychiatric emergency room, particularly synthetic cannabinoid-positive participants. In unadjusted models, cannabinoid-positive participants had lower interferon-γ (IFN-γ) levels (p = 0.046), but this finding was not significant after adjusting for covariates and multiple comparisons. Among cannabinoid-positive participants, IL-6 levels negatively correlated with PANSS total score (p = 0.040), as well as positive (p = 0.035) and negative (p = 0.024) subscales. Results suggest inflammatory alterations among psychotic individuals with comorbid cannabinoid use.

The Relevance of Sex in the Association of Synthetic Cannabinoid Use With Psychosis and Agitation in an Inpatient Population.

BACKGROUND: Current evidence suggests that women are more sensitive to the effects of cannabinoids. The aim of this study was to investigate the relevance of sex in the association of synthetic cannabinoid (SC) use with psychosis and agitation. METHODS: A retrospective chart review was conducted for patients admitted to a psychiatric unit (2014-2016) to extract information on demographic factors, use of substances, clinical symptoms, and pharmacologic treatments. Study groups were defined as SC users (anyone who reported use of SCs over the past 3 months), cannabis users (positive toxicology screen for Δ9-tetrahydrocannabinol [THC]), and controls (those who denied use of SCs over the past 3 months and had negative toxicology for THC). RESULTS: Digital charts of 983 patients were reviewed. A total of 162 subjects reported use of SCs over the past 3 months (76% male), and 292 subjects had positive toxicology screen for THC (67% male). A total of 38.9% of SC users (n = 63) had positive urine toxicology screen for THC. SC users had higher risks of psychotic presentations (adjusted odds ratio [AOR] = 3.390; 95% CI, 1.390-8.267) and agitation (AOR = 4.643; 95% CI, 1.974-10.918) compared to the controls. While women had lower rates of psychosis than men in the cannabis and control groups, the rates were markedly potentiated with SC use to high levels (79%) approximately equal to that seen in men (80%). There was also a significant interaction between SC use and sex for agitation (AOR = 0.308; 95% CI, 0.117-0.808). Female SC users were significantly more agitated than male SC users (73.7% vs 47.6%, respectively, P = .005). CONCLUSIONS: SC users are more likely than nonusers to be psychotic or agitated in an inpatient setting. The potentiated rates of psychosis and agitation with SC use in women suggest that they may have a greater sensitivity to these synthetic compounds.​.

Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial.

OBJECTIVE: Despite the staggering consequences of the opioid epidemic, limited nonopioid medication options have been developed to treat this medical and public health crisis. This study investigated the potential of cannabidiol (CBD), a nonintoxicating phytocannabinoid, to reduce cue-induced craving and anxiety, two critical features of addiction that often contribute to relapse and continued drug use, in drug-abstinent individuals with heroin use disorder. METHODS: This exploratory double-blind randomized placebo-controlled trial assessed the acute (1 hour, 2 hours, and 24 hours), short-term (3 consecutive days), and protracted (7 days after the last of three consecutive daily administrations) effects of CBD administration (400 or 800 mg, once daily for 3 consecutive days) on drug cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder. Secondary measures assessed participants' positive and negative affect, cognition, and physiological status. RESULTS: Acute CBD administration, in contrast to placebo, significantly reduced both craving and anxiety induced by the presentation of salient drug cues compared with neutral cues. CBD also showed significant protracted effects on these measures 7 days after the final short-term (3-day) CBD exposure. In addition, CBD reduced the drug cue-induced physiological measures of heart rate and salivary cortisol levels. There were no significant effects on cognition, and there were no serious adverse effects. CONCLUSIONS: CBD's potential to reduce cue-induced craving and anxiety provides a strong basis for further investigation of this phytocannabinoid as a treatment option for opioid use disorder.

Qualitative Analysis of Attitudes Toward Adult-Child Sexual Activity Among Minor-Attracted Persons.

This study uses qualitative methodology to explore narrative responses to a question regarding the harmful versus beneficial effects of adult-child sex on children. Data were gathered from a survey of self-identified minor-attracted persons (MAPs). Two hundred and sixty-seven survey participants provided narrative responses. Results indicated a significant amount of variability in perceptions of harm and of mitigating or aggravating factors. Understanding the subjective perspectives of MAPs, the range of their attitudes, and the issues that they identify as pertinent is critically important for clinical efficacy in the treatment of pedophilia.