426 K.P. Lindsey et al.
of cannabinoid drugs on brain metabolism. In vivo neuroimaging, in contrast to
autoradiography, utilizes noninvasive techniques such as positron emission to-
mography (PET), single photon emission computed tomography (SPECT), and
magnetic resonance imaging (MRI) to image both the binding and the effects of
drugs within living brain. These techniques are well developed; however, in vivo
imaging of cannabinoid systems is in a very preliminary state. Early results have
been promising yet hard to generalize. Definitive answers to some of the most
important questions about cannabinoid drugs and their effects await development
of suitable in vivo neuroimaging ligands for cannabinoid systems.
KeywordsCannabinoids · Imaging · Metabolism · Blood flow · MRI (magnetic
resonance imaging) · PET (positron emission tomography) · Autoradiography
1
Introduction
Tetrahydrocannabinol (∆^9 -THC; the main psychoactive ingredient of cannabis)
acts at G protein-coupled receptors (CB 1 receptors) that are abundant in specific
brain areas including the cerebellum, hippocampus and outflow nuclei of the basal
ganglia. Investigators have imaged these receptors in cryostat sections of brain and
alsointhelivingbrainsofhumansandanimals.Additionally,theeffectsofcannabi-
noid agonists and antagonists on cerebral metabolism and blood flow have been
visualized. Two major strategies are reviewed, ex vivo autoradiographical imaging,
and in vivo imaging using positron emission tomography (PET), single photon
emission computed tomography (SPECT), or magnetic resonance imaging (MRI).
Autoradiography is a relatively old technique, first used in a biological context
by Lacassagne in 1924 (Rogers 1973). Radioactivity incorporated into tissues can
be used to generate cumulative, spatially accurate representations of the isotope’s
distribution by placing tissue samples in close proximity to a recording medium,
usually, but not always, a photographic emulsion. Due to their invasive nature,
autoradiographic strategies necessitate a preclinical or postmortem focus and
between-subjects experimental designs.
Over the last quarter century, in vivo imaging modalities have been developed
that allow living brains, including the human brain, to be studied in a non-invasive
manner. These modalities include PET which utilizes positron emitting radiotrac-
ers that are now available for a growing range of neurotransmitter receptors as
well as for blood flow and glucose metabolism. PET, as well as the related modality
SPECT, have been used to perform the same general kinds of experiments that
are possible using ex vivo autoradiography (see Sect. 2). However, in addition,
longitudinal and within-subjects experimental designs are possible.
The non-radionuclide modality functional magnetic resonance imaging (fMRI)
is also becoming an important tool for human neuropharmacological studies.
These include evaluation of acute effects of drugs on control subjects and drug-
dependent individuals. Chronic drug use can be evaluated by means of comparing
dependent and non-dependent subjects.