Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence

Kuhns, Lauren; Kroon, Emese; Colyer-Patel, Karis; Cousijn, Janna

doi:10.1007/s00213-021-06001-8

Cited by 35 publications

(14 citation statements)

References 186 publications

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“…Interestingly, a nominally significant association of parental cannabis use disorder PGS on offspring depression was observed, with an estimated regression coefficient twice as large as that of the offspring’s own cannabis use disorder PGS. Consistent evidence supports an epidemiologic association between cannabis use and depression, but the direction of causality and underlying mechanisms are still unclear . Although our findings require further validation, they highlight the potential for genetic nurture to bias naive estimates of PGSs in studies of unrelated individuals.…”

Section: Discussionmentioning

confidence: 85%

Preliminary Evidence for Genetic Nurture in Depression and Neuroticism Through Polygenic Scores

Tubbs

Sham

2023

JAMA Psychiatry

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ImportanceModeling genetic nurture (ie, the effects of parental genotypes through influences on the environment experienced by their children) is essential to accurately disentangle genetic and environmental influences on phenotypic variance. However, these influences are often ignored in both epidemiologic and genetic studies of depression.ObjectiveTo estimate the association of genetic nurture with depression and neuroticism.Design, Setting, and ParticipantsThis cross-sectional study jointly modeled parental and offspring polygenic scores (PGSs) across 9 traits to test for the association of genetic nurture with lifetime broad depression and neuroticism using data from nuclear families in the UK Biobank, with data collected between 2006 and 2019. A broad depression phenotype was measured in 38 702 offspring from 20 905 independent nuclear families, with most of these participants also reporting neuroticism scores. Parental genotypes were imputed from sibships or parent-offspring duos and used to calculate parental PGSs. Data were analyzed between March 2021 and January 2023.Main Outcomes and MeasuresEstimates of genetic nurture and direct genetic regression coefficients on broad depression and neuroticism.ResultsThis study of 38 702 offspring with data on broad depression (mean [SD] age, 55.5 [8.2] years at study entry; 58% female) found limited preliminary evidence for a statistically significant association of genetic nurture with lifetime depression and neuroticism in adults. The estimated regression coefficient of the parental depression PGS on offspring neuroticism (β = 0.04, SE = 0.02, P = 6.63 × 10−3) was estimated to be approximately two-thirds (66%) that of the offspring’s depression PGS (β = 0.06, SE = 0.01, P = 6.13 × 10−11). Evidence for an association between parental cannabis use disorder PGS and offspring depression was also found (β = 0.08, SE = 0.03, P = .02), which was estimated to be 2 times greater than the association between the offspring’s cannabis use disorder PGS and their own depression status (β = 0.04, SE = 0.02, P = .07).Conclusions and RelevanceThe results of this cross-sectional study highlight the potential for genetic nurture to bias results from epidemiologic and genetic studies on depression or neuroticism and, with further replication and larger samples, identify potential avenues for future prevention and intervention efforts.

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Section: Discussionmentioning

confidence: 85%

Preliminary Evidence for Genetic Nurture in Depression and Neuroticism Through Polygenic Scores

Tubbs

Sham

2023

JAMA Psychiatry

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“…Here it is striking that when baseline depression symptoms are considered, the effect of these symptoms on elation was only significant for the THC-dominant condition in our models. This is particularly interesting in the context of recent reviews that support a strong relationship between depression and CUD (Kuhns et al, 2021;Onaemo et al, 2021), with one review also providing support for a bidirectional relationship between the experience of depression and problematic use (Kuhns et al, 2021). However, neither review takes THC potency into account and no other published research specifically examines the role of THC potencies greater than 75%.…”

Section: Discussionmentioning

confidence: 99%

Baseline affective symptomatology moderates acute subjective effects of high potency THC and CBD cannabis concentrates.

Martin‐Willett¹,

Skrzynski²,

Karoly³

et al. 2023

Experimental and Clinical Psychopharmacology

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Highly potent cannabis concentrates are widely available and associated with affective disturbance and cannabis use disorder. Little is known about the effects of concentrated Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) and their relationship to long-term affect. We explored how baseline affective symptoms (anxiety and depression) relate to acute (i.e., immediate or short-term) subjective mood and intoxication effects during naturalistic use of cannabis concentrates. Fifty-four cannabis users (48% female; Mage = 29.87) were assigned to ad libitum use of either a THC-dominant (84.99% THC and THCa, <1% CBD) or CBD-dominant (74.7% CBD, 4.1% CBDa, 4.5% THC and THCa) concentrate. Individuals were assessed at baseline and before, immediately after, and 1 hr after naturalistic use of their assigned product. Models regressed each outcome on time, product condition, baseline affective symptoms, and their interactions. An interaction emerged between condition and baseline depression symptoms on positive mood (F = 9.47, p < .005); higher depression symptom level was associated with higher positive mood with THC-dominant product use. There was an interaction between condition, baseline depression symptoms, and time on negative mood (F = 5.55, p < .01); negative mood decreased with CBD-dominant product use for all depression symptom levels but increased with THC-dominant product use at high levels. Finally, there was an interaction between condition and time on intoxication (F = 3.72, p = .03); the THC-dominant condition was more intoxicated postuse than the CBD-dominant condition. This novel exploratory study suggests that baseline affect moderates the acute effects of ad libitum use of THC and CBD concentrates such that preexisting affective symptoms modulate the intensity of subjective drug experiences.

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“…Modulation of endocannabinoid signaling for neuroprotective and immunomodulatory purposes when disease is already exacerbated may thus lead to negative results. In addition, long‐term heavy cannabis use has negative effects on cognitive functions (Kuhns et al, 2021) that may complicate the interpretation of results and discourage long‐term clinical studies. Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the loss of dopaminergic neurons in motor circuits leading to dyskinesia, bradykinesia, rigidity and constant muscle tremors as well as a range of non‐motor symptoms (cognitive deficits, mood disorders hallucinations, pain, sleep disorders). The main pathological hallmarks of PD are the accumulation of α‐synuclein aggregates and the degeneration of dopaminergic neurons in the substantia nigra pars compacta projecting to the basal ganglia.…”

Section: Endocannabinoid Signaling In Neurological Disordersmentioning

confidence: 99%

Section: Endocannabinoid Signaling In Neurological Disordersmentioning

confidence: 99%

Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells

Bernal‐Chico

Tepavčević

Manterola

et al. 2022

Glia

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The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid Δ 9 -tetrahydrocannabinol (Δ 9 -THC) in late 1980s paved the way for investigations on the effects of cannabis-based therapeutics in brain pathology.Ever since, a wealth of results obtained from studies on human tissue samples and animal models have highlighted a promising therapeutic potential of cannabinoids and endocannabinoids in a variety of neurological disorders. However, clinical success has been limited and major questions concerning endocannabinoid signaling need to be satisfactorily addressed, particularly with regard to their role as modulators of glial cells in neurodegenerative diseases. Indeed, recent studies have brought into the limelight diverse, often unexpected functions of astrocytes, oligodendrocytes, and microglia in brain injury and disease, thus providing scientific basis for targeting glial cells to treat brain disorders. This Review summarizes the current knowledge on the molecular and cellular hallmarks of endocannabinoid signaling in glial cells and its clinical relevance in neurodegenerative and chronic inflammatory disorders.

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Associations between cannabis use, cannabis use disorder, and mood disorders: longitudinal, genetic, and neurocognitive evidence

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Cited by 35 publications

References 186 publications

Preliminary Evidence for Genetic Nurture in Depression and Neuroticism Through Polygenic Scores

Preliminary Evidence for Genetic Nurture in Depression and Neuroticism Through Polygenic Scores

Baseline affective symptomatology moderates acute subjective effects of high potency THC and CBD cannabis concentrates.

Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells

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