Δ9-Tetrahydrocannabinol Induces Dopamine Release in the Human Striatum

Abstract

The influence of cannabis on mental health receives growing scientific and political attention. An increasing demand for treatment of cannabis dependence has refueled the discussion about the addictive potential of cannabis. A key feature of all addictive drugs is the ability to increase synaptic dopamine levels in the striatum, a mechanism involved in their rewarding and motivating effects. However, it is currently unknown if cannabis can stimulate striatal dopamine neurotransmission in humans. Here we show that D9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, induces dopamine release in the human striatum. Using the dopamine D 2 /D 3 receptor tracer [ 11 C]raclopride and positron emission tomography in seven healthy subjects, we demonstrate that THC inhalation reduces [11 C]raclopride binding in the ventral striatum and the precommissural dorsal putamen but not in other striatal subregions. This is consistent with an increase in dopamine levels in these regions. These results suggest that THC shares a potentially addictive property with other drugs of abuse. Further, it implies that the endogenous cannabinoid system is involved in regulating striatal dopamine release. This allows new directions in research on the effects of THC in neuropsychiatric disorders, such as schizophrenia.

The Genetic Basis Of The Comorbidity Between Cannabis Use And Major Depression

“…DRD2 encodes the D2 dopamine receptor and dopamine has previously been implicated in both MDD and addition phenotypes, via its role in motivation and reward [47] and the effects of abused substances (including cannabis) on dopamine levels in the nucleus accumbens [48,49]. NCAM1 encodes a brain-expressed cell adhesion protein [50], known to be involved in the development of the nervous system and neuroplasticity (important in learning and memory, as reviewed by [51]).…”

Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction

“…In humans, PET studies have shown that several drugs [stimulants (Drevets et al 2001;Volkow et al 1999b), nicotine (Brody et al 2009), alcohol (Boileau et al 2003), and marijuana (Bossong et al 2009)] increase DA in dorsal and ventral striatum (where the NAc is located).…”

Interactions of Cannabis and Amphetamine-Type Stimulants

“…Whereas there is general consensus on the primary involvement of DA in the mechanisms supporting METH-induced acute psychotic states [152,153], the role of this neurotransmitter in cannabis-induced psychosis is more controversial. It has been reported that, in schizophrenia patients, doses of THC that exacerbate psychotic symptoms are associated with a rapid reduction of D 2 receptor binding in the ventral striatum and precommissural dorsal putamen [154,155]. However, similar phenomena were not observed in healthy volunteers [156].…”