Marijuana's interaction with brain reward systems: Update 1991

Gardner, Eliot L.; Lowinson, Joyce H.

doi:10.1016/0091-3057(91)90365-9

Cited by 183 publications

(71 citation statements)

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“…Data reported over the years by Gardner and colleagues support the hypothesis that mesocorticolimbic dopamine pathways are activated by THC much like other drugs of abuse (Wise and Rompre 1989). ⌬ 9 THC facilitates reinforcing electrical brain stimulation (Gardner and Lowinson 1991;Gardner et al 1988) and enhances dopamine transmission (Chen et al 1993;Chen et al 1990). A relatively high concentration of cannabinoid receptors is seen in the NAS (Herkenham et al 1991b;Jansen et al 1992;Thomas et al 1992), while dopamine efflux in the NAS is increased by THC (Chen et al 1990).…”

Section: Discussionmentioning

confidence: 54%

Selective Effects of the Endogenous Cannabinoid Arachidonylethanolamide (Anandamide) on Regional Cerebral Blood Flow in the Rat

Stein

Fuller

Edgemond

et al. 1998

Neuropsychopharmacology

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The behavioral profile seen in humans following administration of marijuana has long been a source of intense interest, because the unique syndrome produced does not resemble that seen after any other psychoactive substance. Subjectively, the cannabinoid syndrome in humans includes sensory enhancement, errors in the judgment of time and space, dissociation of ideas, delusions, impulsivity, and hallucinations (Pertwee 1988). For example, individuals often report that while under the influence of cannabis, auditory, gustatory, and visual stimuli often seem more intense and pleasurable; whereas, time often seems to proceed more slowly. Memory loss, especially short-term or working memory, and attentional deficits are also hallmarks of cannabinoid intoxication (Chait and Pierri 1992;Schwartz 1993). The central nervous system mechanisms and sites of action of these cognitive effects are still poorly understood. NO . 6 Regional changes in cerebral blood flow and metabolism are thought to reflect changes in regional neuronal activity (Sokoloff 1981). Because specific cognitive or drug-induced challenges are known to induce regionally specific changes in neuronal activity regional cerebral blood flow (rCBF), and glucose utilization (Sokoloff, 1981), various functional metabolic imaging procedures have been employed in an attempt to understand better marijuana's neuroanatomical sites of action. Mathew and colleagues (Mathew et al. 1989(Mathew et al. , 1992) measured changes in rCBF following acute drug administration. An increase in CBF was seen in experienced versus inexperienced subjects with greater frontal and right hemisphere blood flow seen 30 min after marijuana smoking. These blood flow effects were not related to changes in general circulation, respiration, or plasma tetrahydrocannabinol (THC) concentrations (Mathew and Wilson 1993). In contrast, using intravenous ⌬ 9 THC, the principal psychoactive agent in marijuana, Volkow et al. (1991) reported an increase in glucose utilization (rCMRglu) only in the cerebellum when data were corrected for changes in global metabolism. More recently, in a population of THC abusers, Volkow et al. (1996) demonstrated THC-induced increases in rCMRglu in the orbitofrontal and prefrontal cortex and basal ganglia that correlated with the subjective sense of intoxication. Baseline cerebellar rCMRglu rates were also lower in abusers than control subjects. In contrast to the above studies on human subjects, Margulies and Hammer (1991) reported biphasic, dose-dependent effects of ⌬ 9 THC in most limbic (but not diencephalic/brainstem) regions, with low doses causing an increase and high doses a decrease in rCMRglu. We (Bloom et al. 1997) have also demonstrated heterogenous decreases in rCBF after acute ⌬ 9 THC administration in the rat at doses comparable to the high doses of Margulies and Hammer (1991).Despite these gains in our understanding of the neuroanatomical localization of ⌬ 9 THC's effect upon brain activity, the recent discovery of an endogenous cannabinoid receptor in ...

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Section: Discussionmentioning

confidence: 54%

Selective Effects of the Endogenous Cannabinoid Arachidonylethanolamide (Anandamide) on Regional Cerebral Blood Flow in the Rat

Stein

Fuller

Edgemond

et al. 1998

Neuropsychopharmacology

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“…The subsidiary finding that THC administration speeded responses to gambles with large compared to small gains, while placebo retarded such responses, provides some limited confirmation of the predictionFbased upon evidence that CB 1 activation enhances reward-related processing (Gardner et al, 1988;Gardner and Lowinson, 1991)Fthat THC intake will potentiate attention towards appetitive cues during risky choice.…”

Section: Discussionmentioning

confidence: 99%

“…Third, THC is known to impact on aspects of reward processing by, for example, reducing reward thresholds for operant responding leading to brain-self-stimulation (Gardner et al, 1988;Gardner and Lowinson, 1991). Also, THC also has an indirect action on dopamine neurotransmission in the mesolimbic and mesocortical systems (Ameri, 1999;Gardner and Vorel, 1998;Tanda and Goldberg, 2003;Tanda et al, 1997), suggesting that the acute effects of THC include altered catecholamine activity within the corticolimbic pathways that mediate decision-making cognition (Scarna et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Low Doses of Δ-9 Tetrahydrocannabinol on Reinforcement Processing in the Risky Decision-Making of Young Healthy Adults

Rogers

Wakeley

Robson

et al. 2006

Neuropsychopharmacol

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Research suggests that risky decision-making is sensitive to neuromodulatory influences acting upon corticolimbic circuitry. However, while other evidence attests to effects of D-9 tetrahydrocannabinol (THC) on the activity of reward pathways, relatively little is known about the possible involvement of cannabinoid activity in risky choice. In this experiment, we examined the effects of a single sublingual 5 mg dose of THC on a test of risky decision-making (requiring choices between simultaneously presented gambles differing in their magnitude of gains, magnitude of losses and the probability with which these outcomes were delivered). Tests of non-normative decision-making involving risk-aversion when deciding between gains and risk-seeking choices when deciding between losses were also included. In all, 15 healthy adults were administered 5 mg THC and placebo in a double-blind, placebo-controlled, within-subject, crossover design. THC had three principal effects relative to placebo: (i) THC reduced choice of gambles with variable gains and losses, but increased choice of gambles with zero-expected value; (ii) THC reduced participants' attention towards losses when the probability of winning was low (and the probability of losing was high); and (iii) THC speeded participants' responses to gambles with large compared to small potential gains. These results suggest that THC mediates specific motivational processes and the processing of reinforcement cues during risky choice, perhaps reflecting altered CB 1 receptor or catecholamine activity within corticolimbic pathways.

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“…The actions of D 9 -tetrahydrocannabinol (THC), the active principle of marijuana, and its synthetic analogues have been recently described in central dopaminergic systems. After acute administration, dopamine outflow is increased in the nucleus accumbens (Gardner and Lowinson 1991) and prefrontal cortex (Chen et al 1990) while dopaminergic neuronal activity in anesthetized rats is increased in the VTA and substantia nigra (French 1997;French et al 1997) by an action on CB1 receptors. In unanesthetized rats, cannabinoids similarly activate mesolimbic ) and mesoprefrontal dopaminergic neurons (Diana et al 1998b) by a selective action on CB1 receptors.…”

Section: Acute Effects Of Drugs Of Abuse On Dopaminergic Neuronsmentioning

confidence: 99%