ASSIGNMENT

Students are expected to write down the neuroanatomical and neurochemical properties influence of

1) Caffeine

2) Marijuana

3) Alcohol

CAFFEINE

Caffeine is the most widely consumed psychoactive substance in the world. Caffeine is found in
more than 60 species of plants and belongs to the methylxanthine class of alkaloids, which also includes
theobromine (found in chocolate) and theophylline (often used in the treatment of asthma).

Caffeine, a methylxanthine, is more potent than another commonly used methylxanthine,

theophylline (Primatene). The half-life of caffeine in the human body is 3 to 10 hours, and the time of peak
concentration is 30 to 60 minutes. Caffeine readily crosses the blood–brain barrier. Caffeine acts primarily
as an antagonist of the adenosine receptors. Adenosine receptors activate an inhibitory G protein (Gi) and,
thus, inhibit the formation of the second-messenger cyclic adenosine monophosphate (cAMP). Caffeine
intake, therefore, results in an increase in intraneuronal cAMP concentrations in neurons with adenosine
receptors. Three cups of coffee are estimated to deliver so much caffeine to the brain that about 50 percent
of the adenosine receptors are occupied by caffeine. Several experiments indicate that caffeine, especially at
high doses or concentrations, can affect dopamine and noradrenergic neurons. Specifically, dopamine
activity may be enhanced by caffeine, a hypothesis that could explain clinical reports associating caffeine
intake with an exacerbation of psychotic symptoms in patients with schizophrenia. Activation of
noradrenergic neurons has been hypothesized to be involved in the mediation of some symptoms of caffeine
withdrawal.

MARIJUANA

Cannabis preparations are obtained from the plant Cannabis sativa (Fig. 20.4-1), which has been
used in China, India, and the Middle East for approximately 8,000 years, primarily for its fibres and
secondarily for its medicinal properties. The plant occurs in male and female forms. The female plant
contains the highest concentrations of more than 60 cannabinoids that are unique to the plant.

The principal component of cannabis is Δ9-THC; however, the cannabis plant contains more than 400
chemicals, of which about 60 are chemically related to Δ9-THC. In humans, Δ9-THC is rapidly converted
into 11-hydroxy-Δ9-THC, the metabolite that is active in the central nervous system (CNS). A specific
receptor for the cannabinols has been identified, cloned, and characterized. The cannabinoid receptor, a
member of the G-protein-linked family of receptors, is linked to the inhibitory G protein (Gi), which is
linked to adenylyl cyclase in an inhibitory fashion. The cannabinoid receptor is found in highest
concentrations in the basal ganglia, the hippocampus, and the cerebellum, with lower concentrations in the
cerebral cortex. This receptor is not found in the brainstem, a fact consistent with cannabis’s minimal
effects on respiratory and cardiac functions. Studies in animals have shown that the cannabinoids affect the
monoamine and γ-aminobutyric acid (GABA) neurons.

ALCOHOL

Alcohol is a brain depressant. There are different alcohol beverages ranging from beer, wine,
whiskey, rum, gin, vodka etc. The common factor among all these beverages is that all these contain ethyl
alcohol as the main psychoactive substance. The difference lies in the concentration of ethyl alcohol in these
beverages and the way in which these beverages are prepared. The effect of alcohol depends on the amount
of beverage consumed as well as the speed of consumption of the beverage.

In contrast to most other substances of abuse with identified receptor targets—such as the N-methyl-
D-aspartate (NMDA) receptor of phencyclidine (PCP)—no single molecular target has been identified as the
mediator for the effects of alcohol. The longstanding theory about the biochemical effects of alcohol
concerns its effects on the membranes of neurons. Data support the hypothesis that alcohol produces its
effects by intercalating itself into membranes and, thus, increasing fluidity of the membranes with short-term
use. With long-term use, however, the theory hypothesizes that the membranes become rigid or stiff. The
fluidity of the membranes is critical to normal functioning of receptors, ion channels, and other membrane-
bound functional proteins. In recent studies, researchers have attempted to identify specific molecular targets
for the effects of alcohol. Most attention has been focused on the effects of alcohol at ion channels.
Specifically, studies have found that alcohol ion channel activities associated with the nicotinic
acetylcholine, serotonin 5-hydroxytryptamine3 (5-HT3), and GABA type A (GABAA) receptors are
enhanced by alcohol, whereas ion channel activities associated with glutamate receptors and voltage-gated
calcium channels are inhibited.

NISHITA SRIVASTAVA

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