Kannabis-uutisia englanniksi

Evidence Accumulates for Links Between Marijuana and Psychosis

Michael T. Compton, MD, MPH

Posted: 03/26/2010

Introduction

A number of studies in recent years have revealed complex links between marijuana use and psychotic symptoms and diagnosable psychotic disorders like schizophrenia. Although a thorough review of this broad literature is beyond the purview of this brief communication, two avenues of research will be succinctly summarized, pertaining to (1) associations between cannabis use and clinical manifestations of psychosis, and (2) the biologic plausibility of the observed links.

Cannabis and Psychosis

Diverse studies suggest that cannabis use is associated with psychotic phenomenology. First, in addition to being the most abused illicit substance in the general US population, cannabis is clearly the most abused illegal drug among individuals with schizophrenia.^[1,2] Furthermore, the initiation of cannabis use among those with psychotic disorders often precedes the onset of psychosis by several years.^[1,3,4] Second, cannabis use in adolescence is increasingly recognized as an independent risk factor for psychosis and schizophrenia.^[5-7] That is, several epidemiologic studies suggest that cannabis use is a component cause of schizophrenia.^[8,9] Very recently, McGrath and colleagues^[10] reported that early cannabis use is associated with psychosis-related outcomes (having a nonaffective psychotic disorder, scoring in the highest quartile of the Peters Delusions Inventory,^[11] and reporting hallucinations) in a cohort of 3801 individuals assessed at age 18-23 years. Findings among 228 sibling pairs in that study reduce the likelihood that unmeasured confounding variables account for the results.^[10] Third, cannabis use may interact with genetic factors to elevate risk for psychotic disorders. One sentinel study demonstrated that the catechol-O-methyltransferase Val¹⁵⁸Met functional polymorphism moderates the effects of adolescent-onset cannabis use on the later development of psychosis.^[12] Fourth, preliminary research suggests that cannabis use before the manifestation of psychiatric symptoms may be associated with an earlier age at onset of psychotic symptoms,^[13] and perhaps even an earlier onset of prodromal symptoms.^[14] We found that simply classifying first-episode psychosis patients according to their maximum frequency of use before onset of psychotic symptoms (ie, categorizing into none, ever, weekly, or daily use) revealed no significant effects of cannabis use on risk for onset, but analyzing the change in frequency of use before onset (using time-dependent covariates), revealed that progression to daily cannabis use was associated with age at onset.^[14] Fifth, aside from studies linking cannabis use and psychotic disorders, an increasing body of research suggests a potential association between cannabis use and schizotypal symptoms, or psychosis-proneness, in the general population.^[15,16]

Several lines of evidence support the potential biologic plausibility of these links between cannabis use and psychosis. First, exogenous (eg, Δ-9-tetrahydrocannabinol) and endogenous cannabinoids (eg, anandamide) exert their effects (such as modulating the release of neurotransmitters including dopamine and glutamate) by interactions with specific cannabinoid (CB1) receptors that are distributed in brain regions implicated in schizophrenia. Second, several studies have shown an increased CB1 receptor density in brain regions of interest in schizophrenia, including the dorsolateral prefrontal cortex and the anterior cingulate cortex.^[17,18] Third, other studies report elevated levels of endogenous cannabinoids in the blood and cerebrospinal fluid of patients with schizophrenia.^[19-21] Fourth, acute, controlled administration of Δ-9-tetrahydrocannabinol causes both patients and controls to experience transient increases in cognitive impairments and schizophrenia-like positive and negative symptoms.^[22] In summarizing these and many other findings, Fernandez-Espejo and colleagues^[23] have suggested that the endocannabinoid system is altered in schizophrenia and that dysregulation of this system, perhaps induced by exogenous cannabis, can interact with neurotransmitter systems in a way so that a "cannabinoid hypothesis" can be integrated with other neurobiologic hypotheses (eg, those involving dopamine and glutamate).

Conclusion

In sum, a growing body of clinical and epidemiologic research suggests significant but complex links between cannabis use and psychosis. Concurrently, ongoing neurobiologic research is revealing findings in the endocannabinoid system that appear to support the biologic plausibility of such links. It should be noted that much of the research conducted to date does not allow for causal determinations. Ongoing research of varying designs will undoubtedly enlighten the field

Source: From Medscape Psychiatry & Mental Health

Early Marijuana Use Heightens Psychosis Risk in Young Adults

Allison Gandey

March 4, 2010 (Updated with comment March 10, 2010) — Experimenting with marijuana at a young age increases the risk for hallucinations or delusions later in life, a new study shows.

"Early cannabis use increases the risk of psychosis in young adults," lead investigator John McGrath, MD, from the Queensland Centre for Mental Health Research in Brisbane, Australia, told Medscape Psychiatry.

"Apart from having an increased risk of having a disorder like schizophrenia, the longer the young adults reported since their first cannabis use, the more likely they were to report isolated symptoms of psychosis."

Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks.

Psychotic disorders are common and typically affect 1 or 2 people of every 100. "Despite our best efforts with treatment, not everyone makes a full recovery," Dr. McGrath said. "We need to think about prevention. Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks."

Dr. McGrath says he was surprised that the results were so strong and so consistent.

The study was published online March 1 in Archives of General Psychiatry.

Investigators studied 3800 young adults born at an Australian hospital taking part in the Mater-University Study of Pregnancy.

Prospective studies have already identified an association between marijuana use and later psychosis-related outcomes, but concerns remain about unmeasured confounding variables.

Dr. McGrath and his team focused instead on 228 sibling pairs in the prospective birth cohort to reduce the influence of unmeasured residual confounding.

Investigators followed up study participants at ages 5, 14, and 21 years. The researchers assessed first marijuana use and 3 psychosis-related outcomes. These outcomes included nonaffective disease, hallucinations, and the Peters et al delusions inventory score.

Table. Odds Ratio of Psychosis-Related Outcomes With Marijuana Use

Investigators evaluated all associations between duration of marijuana use and psychosis-related outcomes using logistic regression adjusted for sex, age, parental mental illness, and hallucinations at the 14-year follow-up.

The results mirror those of another study published in the November issue of the American Journal of Psychiatry (2009;166:1251–1257). That work suggests a link between daily cannabis or tobacco use and early-onset psychosis.

In that study, investigators looked at 109 patients in a psychiatric unit and found that daily marijuana and tobacco use was common. More than 40% of patients used one or both substances.

Of those who abused cannabis, almost 88% were classified as weekly or daily users before the onset of psychosis.

Escalating Marijuana Use Hastened Psychosis

It is not clear why escalating marijuana use may hasten psychosis, lead investigator Michael Compton, MD, from the Emory University School of Medicine in Atlanta, Georgia, noted in November. However, studies have shown increased cannabinoid receptor density in areas of the brain and elevated levels of endogenous cannabinoids in the blood of some patients with psychosis.

This new study, Dr. McGrath points out, provides additional evidence that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults.

Asked by Medscape Psychiatry to comment, Emma Barkus, PhD, from the University of Wollongong in New South Wales, Australia, says the findings are consistent with the substance literature, which suggests that those who are engaging in risk behaviors at the age of 14 years are more likely to persist as they get older.

"Despite the restrictions of the methodologies," she noted, "such as use of retrospective recall and the pseudoquantification of cannabis exposure, the sample size and the persistence of the findings in the face of controlling for confounding variables and analyses on subsets of participants lend strength to an area of literature which is still fraught with controversy."

Dr. Barkus says the findings add further support to the role of cannabis use in psychoses in outcomes.

This study was funded by the National Health and Medical Research Council of Australia. Coauthor Dr. Rosa Alati is supported by a National Health and Medical Research Council Career Development Award in Population Health.

Arch Gen Psychiatry. Published online March 1, 2010.