The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research
01 Dec 2018-Vol. 104, Iss: 4, pp 32-32
TL;DR: Despite increased cannabis use and a changing state-level policy landscape, conclusive evidence regarding the shortand long-term health effects—both harms and benefits—of cannabis use remains elusive.
Abstract: Recent years have seen a rapid rise in the medical and recreational use of cannabis: a broad term that can be used to describe the various products and chemical compounds (e.g., marijuana, cannabinoids) derived from different species of the cannabis plant. Despite increased cannabis use and a changing state-level policy landscape, conclusive evidence regarding the shortand long-term health effects—both harms and benefits—of cannabis use remains elusive.
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TL;DR: Both anxious/distressed specifier and mixed-features specifier were associated with early onset, poor course and functioning, and suicidality in US adults, and much remains to be learned about the DSM-5 MDD specifiers in the general population.
Abstract: Importance No US national data are available on the prevalence and correlates of DSM-5 –defined major depressive disorder (MDD) or on MDD specifiers as defined in DSM-5 . Objective To present current nationally representative findings on the prevalence, correlates, psychiatric comorbidity, functioning, and treatment of DSM-5 MDD and initial information on the prevalence, severity, and treatment of DSM-5 MDD severity, anxious/distressed specifier, and mixed-features specifier, as well as cases that would have been characterized as bereavement in DSM-IV . Design, Setting, and Participants In-person interviews with a representative sample of US noninstitutionalized civilian adults (≥18 years) (n = 36 309) who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III). Data were collected from April 2012 to June 2013 and were analyzed in 2016-2017. Main Outcomes and Measures Prevalence of DSM-5 MDD and the DSM-5 specifiers. Odds ratios (ORs), adjusted ORs (aORs), and 95% CIs indicated associations with demographic characteristics and other psychiatric disorders. Results Of the 36 309 adult participants in NESARC-III, 12-month and lifetime prevalences of MDD were 10.4% and 20.6%, respectively. Odds of 12-month MDD were significantly lower in men (OR, 0.5; 95% CI, 0.46-0.55) and in African American (OR, 0.6; 95% CI, 0.54-0.68), Asian/Pacific Islander (OR, 0.6; 95% CI, 0.45-0.67), and Hispanic (OR, 0.7; 95% CI, 0.62-0.78) adults than in white adults and were higher in younger adults (age range, 18-29 years; OR, 3.0; 95% CI, 2.48-3.55) and those with low incomes ($19 999 or less; OR, 1.7; 95% CI, 1.49-2.04). Associations of MDD with psychiatric disorders ranged from an aOR of 2.1 (95% CI, 1.84-2.35) for specific phobia to an aOR of 5.7 (95% CI, 4.98-6.50) for generalized anxiety disorder. Associations of MDD with substance use disorders ranged from an aOR of 1.8 (95% CI, 1.63-2.01) for alcohol to an aOR of 3.0 (95% CI, 2.57-3.55) for any drug. Most lifetime MDD cases were moderate (39.7%) or severe (49.5%). Almost 70% with lifetime MDD had some type of treatment. Functioning among those with severe MDD was approximately 1 SD below the national mean. Among 12.9% of those with lifetime MDD, all episodes occurred just after the death of someone close and lasted less than 2 months. The anxious/distressed specifier characterized 74.6% of MDD cases, and the mixed-features specifier characterized 15.5%. Controlling for severity, both specifiers were associated with early onset, poor course and functioning, and suicidality. Conclusions and Relevance Among US adults, DSM-5 MDD is highly prevalent, comorbid, and disabling. While most cases received some treatment, a substantial minority did not. Much remains to be learned about the DSM-5 MDD specifiers in the general population.
977 citations
TL;DR: Although individual-level risk remains moderate to low and results from this study should be confirmed in future adequately powered prospective studies, the high prevalence of adolescents consuming cannabis generates a large number of young people who could develop depression and suicidality attributable to cannabis.
Abstract: Importance Cannabis is the most commonly used drug of abuse by adolescents in the world. While the impact of adolescent cannabis use on the development of psychosis has been investigated in depth, little is known about the impact of cannabis use on mood and suicidality in young adulthood. Objective To provide a summary estimate of the extent to which cannabis use during adolescence is associated with the risk of developing subsequent major depression, anxiety, and suicidal behavior. Data Sources Medline, Embase, CINAHL, PsycInfo, and Proquest Dissertations and Theses were searched from inception to January 2017. Study Selection Longitudinal and prospective studies, assessing cannabis use in adolescents younger than 18 years (at least 1 assessment point) and then ascertaining development of depression in young adulthood (age 18 to 32 years) were selected, and odds ratios (OR) adjusted for the presence of baseline depression and/or anxiety and/or suicidality were extracted. Data Extraction and Synthesis Study quality was assessed using the Research Triangle Institute item bank on risk of bias and precision of observational studies. Two reviewers conducted all review stages independently. Selected data were pooled using random-effects meta-analysis. Main Outcomes and Measures The studies assessing cannabis use and depression at different points from adolescence to young adulthood and reporting the corresponding OR were included. In the studies selected, depression was diagnosed according to the third or fourth editions ofDiagnostic and Statistical Manual of Mental Disordersor by using scales with predetermined cutoff points. Results After screening 3142 articles, 269 articles were selected for full-text review, 35 were selected for further review, and 11 studies comprising 23 317 individuals were included in the quantitative analysis. The OR of developing depression for cannabis users in young adulthood compared with nonusers was 1.37 (95% CI, 1.16-1.62;I2 = 0%). The pooled OR for anxiety was not statistically significant: 1.18 (95% CI, 0.84-1.67;I2 = 42%). The pooled OR for suicidal ideation was 1.50 (95% CI, 1.11-2.03;I2 = 0%), and for suicidal attempt was 3.46 (95% CI, 1.53-7.84,I2 = 61.3%). Conclusions and Relevance Although individual-level risk remains moderate to low and results from this study should be confirmed in future adequately powered prospective studies, the high prevalence of adolescents consuming cannabis generates a large number of young people who could develop depression and suicidality attributable to cannabis. This is an important public health problem and concern, which should be properly addressed by health care policy.
464 citations
TL;DR: An overview of the changing US epidemiology of cannabis use and associated problems suggests national increases in cannabis potency, prenatal and unintentional childhood exposure; and in adults, increased use, CUD, cannabis-related emergency room visits, and fatal vehicle crashes.
405 citations
TL;DR: It seems unlikely that cannabinoids are highly effective medicines for CNCP, as effects suggest that number needed to treat to benefit is high, and number neededto treat to harm is low, with limited impact on other domains.
Abstract: This review examines evidence for the effectiveness of cannabinoids in chronic noncancer pain (CNCP) and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL, and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 randomised controlled trials (RCTs) and 57 observational studies. Forty-eight studies examined neuropathic pain, 7 studies examined fibromyalgia, 1 rheumatoid arthritis, and 48 other CNCP (13 multiple sclerosis-related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, pooled event rates (PERs) for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo); significant effect for cannabinoids was found; number needed to treat to benefit was 24 (95% confidence interval [CI] 15-61); for 50% reduction in pain, PERs were 18.2% vs 14.4%; no significant difference was observed. Pooled change in pain intensity (standardised mean difference: -0.14, 95% CI -0.20 to -0.08) was equivalent to a 3 mm reduction on a 100 mm visual analogue scale greater than placebo groups. In RCTs, PERs for all-cause adverse events were 81.2% vs 66.2%; number needed to treat to harm: 6 (95% CI 5-8). There were no significant impacts on physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest that number needed to treat to benefit is high, and number needed to treat to harm is low, with limited impact on other domains. It seems unlikely that cannabinoids are highly effective medicines for CNCP.
301 citations
TL;DR: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis.
259 citations
References
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TL;DR: An issue concerning the criteria for tic disorders is highlighted, and how this might affect classification of dyskinesias in psychotic spectrum disorders.
Abstract: Given the recent attention to movement abnormalities in psychosis spectrum disorders (e.g., prodromal/high-risk syndromes, schizophrenia) (Mittal et al., 2008; Pappa and Dazzan, 2009), and an ongoing discussion pertaining to revisions of the Diagnostic and Statistical Manuel of Mental Disorders (DSM) for the upcoming 5th edition, we would like to take this opportunity to highlight an issue concerning the criteria for tic disorders, and how this might affect classification of dyskinesias in psychotic spectrum disorders.
Rapid, non-rhythmic, abnormal movements can appear in psychosis spectrum disorders, as well as in a host of commonly co-occurring conditions, including Tourette’s Syndrome and Transient Tic Disorder (Kerbeshian et al., 2009). Confusion can arise when it becomes necessary to determine whether an observed movement (e.g., a sudden head jerk) represents a spontaneous dyskinesia (i.e., spontaneous transient chorea, athetosis, dystonia, ballismus involving muscle groups of the arms, legs, trunk, face, and/or neck) or a tic (i.e., stereotypic or patterned movements defined by the relationship to voluntary movement, acute and chronic time course, and sensory urges). Indeed, dyskinetic movements such as dystonia (i.e., sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures or positions) closely resemble tics in a patterned appearance, and may only be visually discernable by attending to timing differences (Gilbert, 2006).
When turning to the current DSM-IV TR for clarification, the description reads: “Tic Disorders must be distinguished from other types of abnormal movements that may accompany general medical conditions (e.g., Huntington’s disease, stroke, Lesch-Nyhan syndrome, Wilson’s disease, Sydenham’s chorea, multiple sclerosis, postviral encephalitis, head injury) and from abnormal movements that are due to the direct effects of a substance (e.g., a neuroleptic medication)”. However, as it is written, it is unclear if psychosis falls under one such exclusionary medical disorder. The “direct effects of a substance” criteria, referencing neuroleptic medications, further contributes to the uncertainty around this issue. As a result, ruling-out or differentiating tics in psychosis spectrum disorders is at best, a murky endeavor.
Historically, the advent of antipsychotic medication in the 1950s has contributed to the confusion about movement signs in psychiatric populations. Because neuroleptic medications produce characteristic movement disorder in some patients (i.e. extrapyramidal side effects), drug-induced movement disturbances have been the focus of research attention in psychotic disorders. However, accumulating data have documented that spontaneous dyskinesias, including choreoathetodic movements, can occur in medication naive adults with schizophrenia spectrum disorders (Pappa and Dazzan, 2009), as well as healthy first-degree relatives of chronically ill schizophrenia patients (McCreadie et al., 2003). Taken together, this suggests that movement abnormalities may reflect pathogenic processes underlying some psychotic disorders (Mittal et al., 2008; Pappa and Dazzan, 2009).
More specifically, because spontaneous hyperkinetic movements are believed to reflect abnormal striatal dopamine activity (DeLong and Wichmann, 2007), and dysfunction in this same circuit is also proposed to contribute to psychosis, it is possible that spontaneous dyskinesias serve as an outward manifestation of circuit dysfunction underlying some schizophrenia-spectrum symptoms (Walker, 1994). Further, because these movements precede the clinical onset of psychotic symptoms, sometimes occurring in early childhood (Walker, 1994), and may steadily increase during adolescence among populations at high-risk for schizophrenia (Mittal et al., 2008), observable dyskinesias could reflect a susceptibility that later interacts with environmental and neurodevelopmental factors, in the genesis of psychosis.
In adolescents who meet criteria for a prodromal syndrome (i.e., the period preceding formal onset of psychotic disorders characterized by subtle attenuated positive symptoms coupled with a decline in functioning), there is sometimes a history of childhood conditions which are also characterized by suppressible tics or tic like movements (Niendam et al., 2009). On the other hand, differentiating between tics and dyskinesias has also complicated research on childhood disorders such as Tourette syndrome (Kompoliti and Goetz, 1998; Gilbert, 2006).
We propose consideration of more explicit and operationalized criteria for differentiating tics and dyskinesias, based on empirically derived understanding of neural mechanisms. Further, revisions of the DSM should allow for the possibility that movement abnormalities might reflect neuropathologic processes underlying the etiology of psychosis for a subgroup of patients. Psychotic disorders might also be included among the medical disorders that are considered a rule-out for tics.
Related to this, the reliability of movement assessment needs to be improved, and this may require more training for mental health professionals in movement symptoms. Although standardized assessment of movement and neurological abnormalities is common in research settings, it has been proposed that an examination of neuromotor signs should figure in the assessment of any patient, and be as much a part of the patient assessment as the mental state examination (Picchioni and Dazzan, 2009).
To this end it is important for researchers and clinicians to be aware of differentiating characteristics for these two classes of abnormal movement. For example, tics tend to be more complex than myoclonic twitches, and less flowing than choreoathetodic movements (Kompoliti and Goetz, 1998). Patients with tics often describe a sensory premonition or urge to perform a tic, and the ability to postpone tics at the cost of rising inner tension (Gilbert, 2006). For example, one study showed that patients with tic disorders could accurately distinguish tics from other movement abnormalities based on the subjective experience of some voluntary control of tics (Lang, 1991). Another differentiating factor derives from the relationship of the movement in question to other voluntary movements. Tics in one body area rarely occur during purposeful and voluntary movements in that same body area whereas dyskinesia are often exacerbated by voluntary movement (Gilbert, 2006). Finally, it is noteworthy that tics wax and wane in frequency and intensity and migrate in location over time, often becoming more complex and peaking between the ages of 9 and 14 years (Gilbert, 2006). In the case of dyskinesias among youth at-risk for psychosis, there is evidence that the movements tend to increase in severity and frequency as the individual approaches the mean age of conversion to schizophrenia spectrum disorders (Mittal et al., 2008).
As revisions to the DSM are currently underway in preparation for the new edition (DSM V), we encourage greater attention to the important, though often subtle, distinctions among subtypes of movement abnormalities and their association with psychiatric syndromes.
67,017 citations
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01 Jan 2014
TL;DR: The Newcastle-Ottawa Scale (NOS) as discussed by the authors was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results.
Abstract: Nonrandomised studies, including case-control and cohort studies, can be challenging to implement and conduct. Assessment of the quality of such studies is essential for a proper understanding of nonrandomised studies. The Newcastle-Ottawa Scale (NOS) is an ongoing collaboration between the Universities of Newcastle, Australia and Ottawa, Canada. It was developed to assess the quality of nonrandomised studies with its design, content and ease of use directed to the task of incorporating the quality assessments in the interpretation of meta-analytic results. A 'star system' has been developed in which a study is judged on three broad perspectives: the selection of the study groups; the comparability of the groups; and the ascertainment of either the exposure or outcome of interest for case-control or cohort studies respectively. The goal of this project is to develop an instrument providing an easy and convenient tool for quality assessment of nonrandomised studies to be used in a systematic review.
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TL;DR: There is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life, although evidence for affective outcomes is less strong.
2,057 citations