Elsevier

Biological Psychiatry

Volume 71, Issue 8, 15 April 2012, Pages 677-683
Biological Psychiatry

Priority Communication
Dopamine Release in Chronic Cannabis Users: A [11C]Raclopride Positron Emission Tomography Study

https://doi.org/10.1016/j.biopsych.2011.12.018Get rights and content

Background

Low striatal dopamine 2/3 receptor (D2/3) availability and low ventrostriatal dopamine (DA) release have been observed in alcoholism and cocaine and heroin dependence. Less is known about the dopaminergic system in cannabis dependence. We assessed D2/3 availability and DA release in abstinent cannabis users compared with control subjects and explored relationships to cannabis use history using [11C]raclopride positron emission tomography and an amphetamine challenge paradigm.

Methods

Sixteen recently abstinent, psychiatrically healthy cannabis-using participants (27.3 ± 6.1 years, 1 woman, 15 men) and 16 matched control subjects (28.1 ± 6.7 years, 2 women, 14 men) completed two positron emission tomography scans, before and after injection of intravenous d-amphetamine (.3 mg/kg). Percent change in [11C]raclopride binding after amphetamine (change in nondisplaceable binding potential, ΔBPND) in subregions of the striatum was compared between groups. Correlations with clinical parameters were examined.

Results

Cannabis users had an average consumption of 517 ± 465 estimated puffs per month, indicating mild to moderate cannabis dependence. Neither baseline BPND nor ΔBPND differed from control subjects in any region of interest, including ventral striatum. In cannabis-dependent subjects, earlier age of onset of use correlated with lower [ΔBPND] in the associative striatum when controlling for current age.

Conclusions

Unlike other addictions, cannabis dependence of mild to moderate severity is not associated with striatal DA alterations. However, earlier or longer duration of use is related to lower DA release in the associative striatum. These observations suggest a more harmful effect of use during adolescence; more research is needed to distinguish effects of chronicity versus onset.

Section snippets

Study Population

The study was approved by the Institutional Review Board of the New York State Psychiatric Institute. All participants provided written informed consent. Inclusion criteria for cannabis users (CD) were as follows: age 21 to 55 years; regular cannabis use of at least 5 times per week or meeting DSM-IV criteria for cannabis dependence but no other current or past Axis I disorder (including current nicotine dependence), no or minimal exposure to other drugs of abuse, willingness to detoxify from

Participants

Thirty-one participants with cannabis dependence and one with cannabis abuse, but similar amount and chronicity of use to the dependent participants, were initially enrolled in the study. Seven participants were lost to follow-up or withdrew consent, one participant was disqualified for cerebral vascular malformation, and 7 participants were disqualified due to their inability to abstain from cannabis use (no decrease in urine cannabinoid levels over a period of at least 3 weeks). Seventeen

Discussion

This is the first report to evaluate both D2/3 receptor availability and striatal DA release capacity in chronic cannabis-dependent participants compared with matched control subjects.

Unlike other addictions, such as to alcohol, heroin, cocaine, and methamphetamine (22), chronic cannabis abuse or dependence is not associated with alterations in either of these indices. We therefore confirm the absence of alterations in D2/3 receptors previously reported (37) in a larger cohort and show for the

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