PET Imaging Studies in Rhesus Monkey with the Cannabinoid-1 (CB1) Receptor Ligand [11C]CB-119

Hamill, Terence G.; Lin, Linus S.; Hagmann, William K.; Liu, Ping; Jewell, James P.; Sanabria, Sandra; Eng, Wai-si; Ryan, Christine; Fong, Tung M.; Connolly, Brett; Vanko, Amy; Hargreaves, Richard; Goulet, Mark T.; Burns, H. Donald

doi:10.1007/s11307-008-0194-8

Cited by 16 publications

(6 citation statements)

References 11 publications

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“…Part of this has resulted from a pronounced increase of fundamental neurochemistry knowledge including the identification of the cannabinoid (CB 1 and CB 2 ) receptors, endogenous cannabinoid neurotransmitters, and the enzymes that control their production and elimination. CB 1 is found in the central nervous system structures important for pain (cerebral cortex), movement (globus pallidus, caudate/putamen, cerebellum), reward (substantia nigra), and memory (hippocampus) (Hamill et al, 2009) and also in fat, the liver, pancreas, and skeletal muscle (Mackie, 2008). CB 2 is localized to immune cells (B and T-lymphocytes and macrophages) and in the spleen, tonsils, gastrointestinal tract (Guzman, 2003), as well as some immune cells in the brain (Pertwee, 2009).…”

Section: Introductionmentioning

confidence: 99%

Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep

DeKeuster²,

et al. 2017

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A prior epidemiological study identified a reduction in opioid overdose deaths in US states that legalized medical cannabis (MC). One theory to explain this phenomenon is a potential substitution effect of MC for opioids. This study evaluated whether this substitution effect of MC for opioids also applies to other psychoactive medications. New England dispensary members ( n = 1,513) completed an online survey about their medical history and MC experiences. Among respondents that regularly used opioids, over three-quarters (76.7%) indicated that they reduced their use since they started MC. This was significantly ( p < 0.0001) greater than the patients that reduced their use of antidepressants (37.6%) or alcohol (42.0%). Approximately two-thirds of patients decreased their use of anti-anxiety (71.8%), migraine (66.7%), and sleep (65.2%) medications following MC which significantly ( p < 0.0001) exceeded the reduction in antidepressants or alcohol use. The patient's spouse, family, and other friends were more likely to know about their MC use than was their primary care provider. In conclusion, a majority of patients reported using less opioids as well as fewer medications to treat anxiety, migraines, and sleep after initiating MC. A smaller portion used less antidepressants or alcohol. Additional research is needed to corroborate these self-reported, retrospective, cross-sectional findings using other data sources.

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Section: Introductionmentioning

confidence: 99%

Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep

DeKeuster²,

et al. 2017

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“…The recent availability of a positron emission tomography (PET) tracer for in vivo brain imaging of the CB 1 receptor in humans and monkeys [214,215] affords a unique opportunity to test the specific role of this receptor in the vulnerability to the subjective responses to cannabis. Indeed, these ligands have already been employed to show gender differences in CB 1 expression of healthy probands [216], and document an association between low CB 1 receptor density and novelty-seeking personality trait [217].…”

Section: Discussionmentioning

confidence: 99%

Vulnerability Factors for the Psychiatric and Behavioral Effects of Cannabis

2010

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Cogent evidence shows that cannabis plays a variable role on behavioral regulation and the pathophysiology of most psychiatric conditions. Accordingly, cannabis has been alternatively shown to exacerbate or ameliorate mental symptoms, depending on its composition and route of consumption, as well as specific individual and contextual characteristics. The vulnerability to the psychological effects of cannabis is influenced by a complex constellation of genetic and environmental factors. In the present article, we will review the current evidence on the pharmacological, individual and situational factors that have been documented to affect the behavioral and psychiatric effects of cannabinoids.

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“…In the preclinical setting, a wide range of CB 1 -selective radioligands have been used successfully in vitro, such as [ 3 H]CP-55,940 ( Devane et al, 1988, 1992 ), [ 3 H]SR141716A ( Petitet et al, 1996 ), and [ 35 S]GTPγS ( Griffin et al, 1998 ); and also in vivo, such as (−)-5′-[ 18 F]-Δ 8 -THC ( Charalambous et al, 1991 ), [ 123 I]AM251 ( Gatley et al, 1996 ), [ 123 I]AM281 ( Gatley et al, 1998 ), [ 11 C]OMAR ([ 11 C]JHU75528) ( Horti et al, 2006 ), [ 11 C]MePPEP ( Yasuno et al, 2008 ), [ 11 C]/[ 18 F]-PipISB ( Finnema et al, 2009 ) and [ 11 C]CB-119 ( Hamill et al, 2009 ). In vivo human brain CB 1 availability has recently become quantifiable with PET and the use of tracers such as [ 18 F]MK-9470 ( Burns et al, 2007 ), [ 11 C]OMAR ( Wong et al, 2010 ), [ 11 C]MePPEP ( Terry et al, 2009 ), and [ 18 F]FMPEP- d 2 ( G.E.…”

Section: Introductionmentioning

confidence: 99%

Test–retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [11C]MePPEP

et al. 2014

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BackgroundEndocannabinoids are involved in normal cognition, and dysfunction in cannabinoid-receptor-mediated neurotransmission has been suggested in a variety of neurological and psychiatric pathologies. The type 1 cannabinoid receptor (CB1) is widely expressed in the human central nervous system. The objective of this study was to quantify the test–retest reproducibility of measures of the PET ligand [11C]MePPEP in order to assess the stability of CB1-receptor quantification in humans in vivo.MethodsFifteen healthy subjects (eight females; median age 32 years, range 25 to 65 years) had a 90-minute PET scan on two occasions after injection of a median dose of [11C]MePPEP of 364 MBq. Metabolite-corrected arterial plasma input functions were obtained for all scans. Eight ROIs, reflecting different levels of receptor densities/concentrations, were defined automatically: hippocampus, anterior cingulate gyrus, inferior frontal gyrus, caudate nucleus, globus pallidus, nucleus accumbens, thalamus, and pons. We used seven quantification methods: reversible compartmental models with one and two tissue classes, two and four rate constants, and a variable blood volume term (2kbv; 4kbv); model-free (spectral) analyses with and without regularisation, including one with voxel-wise quantification; the simplified reference tissue model (SRTM) with pons as a pseudo-reference region; and modified standard uptake values (mSUVs) calculated for the period of ~ 30–60 min after injection. Percentage test–retest change and between-subject variability were both assessed, and test–retest reliability was quantified by the intraclass correlation coefficient (ICC). The ratio of binding estimates pallidum:pons served as an indicator of a method's ability to reflect binding heterogeneity.ResultsNeither the SRTM nor the 4kbv model produced reliable measures, with ICCs around zero. Very good (> 0.75) or excellent (> 0.80) ICCs were obtained with the other methods. The most reliable were spectral analysis parametric maps (average across regions ± standard deviation 0.83 ± 0.03), rank shaping regularised spectral analysis (0.82 ± 0.05), and the 2kbv model (0.82 ± 0.09), but mSUVs were also reliable for most regions (0.79 ± 0.13). Mean test–retest changes among the five well-performing methods ranged from 12 ± 10% for mSUVs to 16% for 2kbv. Intersubject variability was high, with mean between-subject coefficients of variation ranging from 32 ± 13% for mSUVs to 45% for 2kbv. The highest pallidum:pons ratios of binding estimates were achieved by mSUV (4.2), spectral analysis-derived parametric maps (3.6), and 2kbv (3.6).ConclusionQuantification of CB1 receptor availability using [11C]MePPEP shows good to excellent reproducibility with several kinetic models and model-free analyses, whether applied on a region-of-interest or voxelwise basis. Simple mSUV measures were also reliable for most regions, but do not allow fully quantitative interpretation. [11C]MePPEP PET is well placed as a tool to investigate CB1-receptor mediated neurotransmission in he...

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PET Imaging Studies in Rhesus Monkey with the Cannabinoid-1 (CB1) Receptor Ligand [11C]CB-119

Abstract: [(11)C]CB-119 is a suitable tracer for imaging central CB1 receptors.

Cited by 16 publications

References 11 publications

Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep

Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep

Vulnerability Factors for the Psychiatric and Behavioral Effects of Cannabis

Test–retest reproducibility of cannabinoid-receptor type 1 availability quantified with the PET ligand [11C]MePPEP

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