Striatal D2/D3 receptor availability is inversely correlated with cannabis consumption in chronic marijuana users

Albrecht, Daniel; Skosnik, Patrick D.; Vollmer, Jennifer M.; Brumbaugh, Margaret S.; Perry, Kevin M.; Mock, Bruce H.; Zheng, Qi; Federici, Lauren A.; Patton, Elizabeth A.; Herring, Christine M.; Yoder, Karmen K.

doi:10.1016/j.drugalcdep.2012.07.016

Cited by 56 publications

(50 citation statements)

References 53 publications

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“…We also corroborate prior findings (14)(15)(16) of no significant differences in baseline striatal D2/D3 receptor availability between controls and marijuana abusers and provide preliminary evidence of abnormal midbrain DA reactivity in marijuana abusers.…”

Section: Discussionsupporting

confidence: 89%

“…Only four brain imaging studies (totaling 42 marijuana abusers) have measured DA D2/ D3 receptors (14)(15)(16)42). These studies showed no differences in striatal D2/D3 receptors between marijuana abusers and controls, but their generalizability is limited by the small sample sizes (samples ranged from n = 6 to n = 16).…”

Section: Discussionmentioning

confidence: 99%

“…Imaging studies of the brain DA system in marijuana abusers have also shown different findings from those reported for other types of substance abusers. Specifically, substance abusers (cocaine, methamphetamine, alcohol, heroin, and nicotine), but not marijuana abusers (14)(15)(16), show reduced baseline availability of DA D2 receptors in striatum (reviewed ref. 6).…”

mentioning

confidence: 99%

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Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

Volkow

Wang

Telang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

195

147

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Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [ 11 C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral ("self-reports" for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [ 11 C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BP ND )] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BP ND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.nucleus accumbens | amotivation | cannabinoid 1 receptors | brain imaging | midbrain D espite the high prevalence of marijuana consumption, the effects of marijuana abuse in the human brain are not well understood. Marijuana, like other drugs of abuse, stimulates brain dopamine (DA) signaling in the nucleus accumbens (1, 2), which is a mechanism believed to underlie the rewarding effects of drugs (3-5) and to trigger the neuroadaptations that result in addiction (reviewed in ref. 6). Indeed, in humans, imaging studies have shown that drugs of abuse increase DA release in striatum (including the nucleus accumbens), and these increases have been associated with the subjective experience of reward (7-9). However, for marijuana, the results have been inconsistent: One study reported striatal DA increases during intoxication (10); two studies showed no effects (11, 12); and one study reported DA increases in individuals with a psychotic disorder and in their relatives, but not in controls (13). Imaging studies of the brain DA system in marijuana abusers have also shown different findings from those reported for other types of substance abusers. Specifically, substance abusers (cocaine, methamphetamine, alcohol, heroin, and nicotine), but not marijuana abusers (14-16), show reduced baseline availability ...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

Volkow

Wang

Telang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

195

147

View full text Add to dashboard Cite

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“…We included eight case-control studies comparing resting rCBF in adult chronic cannabis users and non cannabis using healthy controls ( [163]. Functional differences between groups were found in all studies, except for the four [ 11 C]-raclopride-PET studies [159][160][161][162]. Abstinence periods ranged from 12 hours to 542 days (for details see Table 2).…”

Section: Structural Neuroimaging Studies In Adolescent Chronic Cannabmentioning

confidence: 99%

“…11 C]-raclopride-PET studies [160][161][162] failed to find any differences between groups in dopamine D2/D3 receptor availability in the striatum as a whole or it functional subdivisions. However, while Stokes [169] used fMRI to compare a visualattention task in current and abstinent cannabis users with healthy controls.…”

mentioning

confidence: 94%

1301 – Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings

Batalla

Bhattachayyria

Yücel

et al. 2013

European Psychiatry

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Background:The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents.

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Genetic Predisposition vs Individual-Specific Processes in the Association Between Psychotic-like Experiences and Cannabis Use

et al. 2019

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Importance: Previous research indicates that cannabis use is associated with psychotic-like experiences (PLEs). Yet is unclear whether this relationship is due to predispositional (i.e., shared genetic) or individual-specific (e.g., causal processes, such as cannabis use leading to PLEs) factors. Objective: To estimate genetic and environmental correlations between cannabis use and PLEs, and to examine PLEs in twins/siblings discordant for exposure to cannabis use to disentangle predispositional from individual-specific effects. Design: Cross-sectional diagnostic interviews and self-report data were collected from two separate population-based samples. Setting: Data from the Human Connectome Project (HCP) were collected between 2012–2015 and data from the Australian Twin Registry Sample 3 (ATR3) were collected between 2005–2009. Participants: The study included data from 1,188 HCP participants and 3,486 ATR3 participants, totaling 4,674 participants. Main Outcomes and Measures: Three cannabis involvement variables were examined: frequent use (i.e., ≥100 times), a DSM-IV lifetime cannabis use disorder (CUD) diagnosis, and current cannabis use. Genetic and environmental correlations between cannabis involvement and PLEs were estimated. Generalized linear mixed models examined PLE differences in twin/sibling pairs discordant for cannabis use. Results: Analyses were performed in 4,674 participants (mean age=30.51 years, 62.5% female). PLEs were associated with frequent use (β=0.11; 95% CI, 0.08–0.14), CUD (β=0.13; 95% CI, 0.09–0.16), and current cannabis use (β=0.07; 95% CI, 0.04–0.10), even after adjustment for covariates. Correlated genetic factors explained between 69.2–84.1% of this observed association. Even so, within discordant pairs of twins/siblings (Npairs: 308–324), PLEs were more common in cannabis exposed individuals relative to their relative who used cannabis to a lesser degree (βs≥.23, ps<.05; e.g., mean PLE score difference between frequent and infrequent cannabis-using relatives=0.27, Z=−5.41, p<.001). Conclusions: Despite the strong contribution of shared genetic factors, frequent and problem cannabis use also relates to PLEs via person-specific pathways. Policy discussions surrounding legalization should consider the impact of escalations in cannabis use on trait-like indices of vulnerability, like PLEs, which could contribute to pervasive psychological and interpersonal burden.

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Striatal D2/D3 receptor availability is inversely correlated with cannabis consumption in chronic marijuana users

Cited by 56 publications

References 53 publications

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

1301 – Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings

Genetic Predisposition vs Individual-Specific Processes in the Association Between Psychotic-like Experiences and Cannabis Use

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