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Further human evidence for striatal dopamine release induced by administration of ?9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

ABSTRACT: RATIONALE:Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ?9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. OBJECTIVES:The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. METHODS:We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n?=?7 and n?=?13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. RESULTS:THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39?±?0.26 to 2.30?±?0.23, p?=?0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. CONCLUSIONS:In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

SUBMITTER: Bossong MG

PROVIDER: S-EPMC4816196 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

Bossong Matthijs G MG Mehta Mitul A MA van Berckel Bart N M BN Howes Oliver D OD Kahn René S RS Stokes Paul R A PR

Psychopharmacology 20150325 15

<h4>Rationale</h4>Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. ...[more]

PMID: 25801289

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Project description:Delta-9-tetrahydrocannabinol (?9-THC) is a naturally occurring psychoactive compound derived from the hemp plant Cannabis sativa. In 2015, EFSA established an acute reference dose (ARfD) of 1 ?g/kg body weight (bw) for ?9-THC and assessed acute dietary exposure from milk and dairy products. This resulted at the most 3% and 13% of the ARfD for adults and toddlers, respectively. Following the European Commission Recommendation 2016/2115 on the monitoring of the presence of ?9-THC in food and the issuing of a new mandate, EFSA assessed the acute human exposure to ?9-THC. 'Standard' food categories were used as proxies for consumption of hemp and hemp-based products. Twelve independent scenarios based on single food categories were considered and acute exposure was assessed for consumption days only for all age groups excluding infants. Occurrence data for Total-?9-THC (588 samples in total) were used for this assessment up to the highest reliable percentile for each food category. The EFSA ARfD of 1 ?g/kg bw was exceeded in the adult high consumers of most considered hemp and hemp-containing products, under the lower-bound (LB) and upper-bound (UB) scenario. At the UB, acute exposure in adult high consumers was estimated based on the highest reliable percentile of occurrence, for Hemp seeds (P95, up to 9 ?g/kg bw), Hemp oil (P95, up to 21 ?g/kg bw), Tea (Infusion) (P95, up to 208 ?g/kg bw), Breakfast cereals (P50, up to 1.3 ?g/kg bw), Pasta (Raw) (P75, up to 6.4 ?g/kg bw), Bread and rolls (P75, up to 1.3 ?g/kg bw), Bread and rolls from hemp flour (P90, up to 4.1 ?g/kg bw), Cereal bars (P50, up to 0.3 ?g/kg bw), Fine bakery wares (P75, up to 5.1 ?g/kg bw), Chocolate (Cocoa) products (P75, up to 1.1 ?g/kg bw), Energy drinks (P75, up to 0.2 ?g/kg bw), Dietary supplements (P75, up to 9.9 ?g/kg bw), Beer and beer-like beverages (P90, up to 41 ?g/kg bw). The use of proxies for the consumption of hemp and hemp-containing products, the limited number of occurrence data and the analytical limitations in the quantification of ?9-THC represent the most important sources of uncertainty. Overall, exposure estimates presented in this report are expected to represent an overestimation of acute exposure to ?9-THC in the EU.

Dataset Information

Further human evidence for striatal dopamine release induced by administration of ?9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

Publications

Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

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