Pharmacotherapies for cannabis dependence.
Ontology highlight
ABSTRACT:
SUBMITTER: Nielsen S
PROVIDER: S-EPMC6360924 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC4297244 | biostudies-literature
Project description:Cannabis is the most widely used and variably regulated drug in the world, with increasing trends of use being reported in the US, Australia, Asia, and Africa. Evidence has shown a decrease in the age of commencement of cannabis use in some developed countries and a prolongation of risk of initiation to cannabis use beyond adolescence among more recent users. Cannabis use is associated with numerous health risks and long-term morbidity, as well as risk of developing cannabis-use disorders. Cannabis users infrequently seek professional treatment, and normally do so after a decade of use. Cannabis-use disorders are currently treated using a selection of psychosocial interventions. Severity of withdrawal is a factor that increases the risk of relapse, and is the target of pharmacotherapy studies. Currently, there is no approved pharmacotherapy for cannabis-use disorders. A number of approaches have been examined, and trials are continuing to find a safe and effective medication with little abuse liability.
| S-EPMC4862355 | biostudies-literature
Project description:Cannabis is a major substance of abuse, and the gene encoding for the central cannabinoid receptor (CNR1) is a logical candidate gene for vulnerability toward developing symptoms of cannabis dependence. We studied four single-nucleotide polymorphisms (SNPs) in the CNR1 gene for association with having one or more symptoms of cannabis dependence in 541 adolescent subjects who had all tried cannabis five or more times. Cases (327) were defined as those who had tried marijuana and developed one or more symptoms, and controls (214) as those who had tried marijuana but developed no dependence symptoms. Cannabis dependence symptoms were assessed in these youth when they were 17 or older with the Composite International Diagnostic Interview--Substance Abuse Module. Univariate (single-marker) association tests demonstrated that SNP rs806380, located in intron 2 of the CNR1 gene, was significantly associated with developing one or more cannabis dependence symptoms, with the G allele having a protective effect (P < 0.02). This was consistent with the results of the global haplotype test (P < 0.01). One of the common haplotypes examined (present in 21% of the subjects) was significantly associated with a lower rate of having one or more cannabis dependence symptoms. Our findings provide evidence suggesting that a common CNR1 haplotype is associated with developing fewer cannabis dependence symptoms among adolescents who have experimented with cannabis.
| S-EPMC2564870 | biostudies-literature
Project description:BACKGROUND:Cannabis abuse (CA) has been associated with psychopathology, including negative emotionality and higher risk of psychosis, particularly with early age of initiation. However, the mechanisms underlying this association are poorly understood. Because aberrant dopamine signaling is implicated in cannabis-associated psychopathology, we hypothesized that regular CA would be associated with altered resting-state functional connectivity in dopamine midbrain-striatal circuits. METHODS:We examined resting-state brain activity of subcortical regions in 441 young adults from the Human Connectome Project, including 30 subjects with CA meeting DSM-IV criteria for dependence and 30 control subjects matched on age, sex, education, body mass index, anxiety, depression, and alcohol and tobacco usage. RESULTS:Across all subjects, local functional connectivity density hubs in subcortical regions were most prominent in ventral striatum, hippocampus, amygdala, dorsal midbrain, and posterior-ventral brainstem. As hypothesized, subjects with CA showed markedly increased local functional connectivity density relative to control subjects, not only in ventral striatum (where nucleus accumbens is located) and midbrain (where substantia nigra and ventral tegmental nuclei are located) but also in brainstem and lateral thalamus. These effects were observed in the absence of significant differences in subcortical volumes and were most pronounced in individuals who began cannabis use earliest in life and who reported high levels of negative emotionality. CONCLUSIONS:Together, these findings suggest that chronic CA is associated with changes in resting-state brain function, particularly in dopaminergic nuclei implicated in psychosis but that are also critical for habit formation and reward processing. These results shed light on neurobiological differences that may be relevant to psychopathology associated with cannabis use.
| S-EPMC5833305 | biostudies-literature
Project description:Cannabis has been legalised for medical use in an ever-increasing number of countries. A growing body of scientific evidence supports the use of medical cannabis for a range of therapeutic indications. In parallel with these developments, concerns have been expressed by many prescribers that increased use will lead to patients developing cannabis use disorder. Cannabis use disorder has been widely studied in recreational users, and these findings have often been projected onto patients using medical cannabis. However, studies exploring medical cannabis dependence are scarce and the appropriate methodology to measure this construct is uncertain. This article provides a narrative review of the current research to discern if, how and to what extent, concerns about problems of dependence in recreational cannabis users apply to prescribed medical users. We focus on the main issues related to medical cannabis and dependence, including the importance of dose, potency, cannabinoid content, pharmacokinetics and route of administration, frequency of use, as well as set and setting. Medical and recreational cannabis use differs in significant ways, highlighting the challenges of extrapolating findings from the recreational cannabis literature. There are many questions about the potential for medical cannabis use to lead to dependence. It is therefore imperative to address these questions in order to be able to minimise harms of medical cannabis use. We draw out seven recommendations for increasing the safety of medical cannabis prescribing. We hope that the present review contributes to answering some of the key questions surrounding medical cannabis dependence.
| S-EPMC8278552 | biostudies-literature
Project description:Most drugs of abuse lead to a general blunting of dopamine release in the chronic phase of dependence, which contributes to poor outcome. To test whether cannabis dependence is associated with a similar dopaminergic deficit, we examined striatal and extrastriatal dopamine release in severely cannabis-dependent participants (CD), free of any comorbid conditions, including nicotine use. Eleven CD and 12 healthy controls (HC) completed two positron emission tomography scans with [11C]-(+)-PHNO, before and after oral administration of d-amphetamine. CD stayed inpatient for 5-7 days prior to the scans to standardize abstinence. Magnetic resonance spectroscopy (MRS) measures of glutamate in the striatum and hippocampus were obtained in the same subjects. Percent change in [11C]-(+)-PHNO-binding potential (?BPND) was compared between groups and correlations with MRS glutamate, subclinical psychopathological and neurocognitive parameters were examined. CD had significantly lower ?BPND in the striatum (P=0.002, effect size (ES)=1.48), including the associative striatum (P=0.003, ES=1.39), sensorimotor striatum (P=0.003, ES=1.41) and the pallidus (P=0.012, ES=1.16). Lower dopamine release in the associative striatum correlated with inattention and negative symptoms in CD, and with poorer working memory and probabilistic category learning performance in both CD and HC. No relationships to MRS glutamate and amphetamine-induced subclinical positive symptoms were detected. In conclusion, this study provides evidence that severe cannabis dependence-without the confounds of any comorbidity-is associated with a deficit in striatal dopamine release. This deficit extends to other extrastriatal areas and predicts subclinical psychopathology.
| S-EPMC5033654 | biostudies-literature
Project description:BackgroundCannabis use disorder (CUD) has been linked to personality disorders (PDs) and interpersonal problems, though these relationships have been understudied. We examined PDs and social support associated with cannabis dependence and how it may be distinguishable from alcohol dependence on these indices in a large representative sample.MethodData on social support and Diagnostic and Statistical Manual of Mental Disorders-IV substance dependence and PDs were assessed in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (N > 34,500).ResultsCannabis dependence was associated with higher rates of personality disorders and lower social support. Lifetime cannabis dependence without alcohol dependence was associated with higher rates of all PDs than alcohol dependence without cannabis dependence (with the exception of borderline PD). Cannabis dependence alone was also associated with lower social support than alcohol dependence alone.LimitationsThe survey was conducted in 2004-2005 and relied on DSM-IV criteria.ConclusionsThese findings highlight a broad range of PDs as well as deficits in social support in cannabis dependence. The potential interrelationships between interpersonal dysfunction and CUD as well as the relevance of PDs to treatment for CUD warrant further research.
| S-EPMC7065916 | biostudies-literature
Project description:Cannabis use is rising, yet there is poor understanding of biological processes that might link chronic cannabis use to brain structural abnormalities. To lend insight into this topic, we examined white matter microstructural integrity and gray matter cortical thickness/density differences between 89 individuals with cannabis dependence (CD) and 89 matched controls (64 males, 25 females in each group) from the Human Connectome Project. We tested whether cortical patterns for expression of genes relevant for cannabinoid signaling (from Allen Human Brain Atlas postmortem tissue) were associated with spatial patterns of cortical thickness/density differences in CD. CD had lower fractional anisotropy than controls in white matter bundles innervating posterior cingulate and parietal cortex, basal ganglia, and temporal cortex. The CD group also had significantly less gray matter thickness and density in precuneus, relative to controls. Sibling-pair analysis found support for causal and graded liability effects of cannabis on precuneus structure. Spatial patterns of gray matter differences in CD were significantly associated with regional differences in monoacylglycerol lipase (MAGL) expression in postmortem brain tissue, such that regions with higher MAGL expression (but not fatty-acid amide hydrolase or FAAH) were more vulnerable to cortical thinning. In sum, chronic cannabis use is associated with structural differences in white and gray matter, which was most prominent in precuneus and associated white matter tracts. Regions with high MAGL expression, and therefore with potentially physiologically restricted endogenous cannabinoid signaling, may be more vulnerable to the effects of chronic cannabis use on cortical thickness.
| S-EPMC7200265 | biostudies-literature
Project description:Objectives:To identify among Canadian adults who have ever been dependent upon cannabis, the prevalence of risk and protective factors associated with (1) cannabis remission, (2) the absence of psychiatric disorders or addictions in the past year (APD), and (3) positive mental health (PMH). Method:Data from Statistics Canada's nationally representative 2012 Canadian Community Health Survey-Mental Health (n = 20, 777, of whom 336 have a history of cannabis dependence) was used. Chi-square tests and logistic regression analyses were conducted. The World Health Organization Composite International Diagnostic Interview (WHO-CIDI) measures were used to determine lifetime cannabis dependence, past-year remission from cannabis depression, and the absence of psychiatric disorders in the past year (APD) (i.e., no suicidal ideation, depressive episodes, anxiety disorders, bipolar disorders, or any substance dependence). PMH is comprised of three factors: APD, happiness or life satisfaction and social and psychological well-being. Results:Among those with a history of cannabis dependence, 72% were in remission from cannabis dependence. Although 53% were free of major psychiatric disorders and any substance dependence and 43% of respondents were in PMH, these percentages were dramatically lower than those without a history of cannabis dependence (92% and 74%, respectively). Positive outcomes were more common among women, older respondents, those with higher levels of social support, and those who had never had major depressive disorder or generalized anxiety disorder. Conclusion:Although many Canadians with a history of cannabis dependence achieve remission and a large minority are truly resilient and achieve PMH, many are failing to thrive. Targeted outreach is warranted for the most vulnerable individuals with a history of cannabis dependence (e.g., men, younger respondents, those with low social support and a history of mental illness).
| S-EPMC7180401 | biostudies-literature
Project description:Addiction is characterized by an erosion of cognitive control toward drug taking that is accentuated by negative emotional states. Here we tested the hypothesis that enhanced interference on cognitive control reflects a loss of segregation between cognition and emotion in addiction. We analyzed Human Connectome Project data from 1206 young adults, including 89 with cannabis dependence (CD). Two composite factors, one for cognition and one for emotion, were derived using principal component (PC) analyses. Component scores for these PCs were significantly associated in the CD group, such that negative emotionality correlated with poor cognition. However, the corresponding component scores were uncorrelated in matched controls and nondependent recreational cannabis users (n?=?87). In CD, but not controls or recreational users, functional magnetic resonance imaging activations to emotional stimuli (angry/fearful faces?>?shapes) correlated with activations to cognitive demand (working memory; 2-back?>?0-back). Canonical correlation analyses linked individual differences in cognitive and emotional component scores with brain activations. In CD, there was substantial overlap between cognitive and emotional brain-behavior associations, but in controls, associations were more restricted to the cognitive domain. These findings support our hypothesis of impaired segregation between cognitive and emotional processes in CD that might contribute to poor cognitive control under conditions of increased emotional demand.
| S-EPMC7306169 | biostudies-literature