MARIJUANA
The hemp plant, or cannabis (Cannabis sativa), contin-ues to be the
most frequently abused illicit substance in America. The dried leaves and
flowering tops of the plant are referred to as marijuana, and it is typically
smoked in pipes or rolled as cigarettes. It also may be consumed in baked
goods. Hashish is a solid black
resinous material obtained from the leaves of the plant and is usually smoked
in a pipe.
The major psychoactive
constituent in marijuana use is 9-tetrahydrocannabinol (THC), the
prototypical can-nabinoid. Although marijuana contains a large number of
cannabinoids, they lack behavioral activity with the exception of cannabinol,
which is approximately one-tenth as potent as THC. The THC content in hashish
is more than double that in marijuana.
∆9-THC is readily absorbed when
marijuana is smoked. Pharmacological effects are produced rapidly and
gener-ally peak within 30 minutes of the onset of smoking. The dynamics of
smoking (number of puffs, spacing, hold time, and lung capacity) substantially influence
how much drug is absorbed. Although oral ingestion of mari-juana produces
similar pharmacological effects, ∆9-THC is absorbed more slowly than by smoking.
Impairment on various performance measures related to driving skills has been
demonstrated immediately following marijuana smoking and up to 24 hours
thereafter. Generally, behav-ioral and physiological effects return to baseline
levels 4 to 6 hours after usage. Blood concentrations of ∆9-THC peak prior to
drug-induced effects. This time discordance between blood concentrations of ∆9-THC and effects has made it
difficult to establish a meaningful relationship between blood concentrations
and effects.
∆9-THC is rapidly distributed
to all tissues despite being tightly bound by plasma proteins. ∆9-THC is a highly lipophilic
substance and so accumulates in tissue high in lipid content. Traces of ∆9-THC have been found in
adipose tissue more than 30 days after the subject smoked a single joint. The
terminal half-life of ∆9-THC in plasma ranges from 18
hours to 4 days.
A cannabinoid receptor
identified in the brain of sev-eral species, including humans, is termed CB1. It is one of the most abundant
receptors in the CNS, and its dis-tribution within the brain reflects the
pharmacological effects produced by ∆9-THC. High receptor densities in the
extrapyramidal motor system and the cerebellum are consistent with the actions
of cannabinoids on many forms of movement. The effects of cannabinoids on
cog-nition and memory may be due to the relatively dense receptor populations
in the hippocampus and cortex. The presence of cannabinoid receptors in the
ventro-medial striatum and nucleus accumbens suggests an as-sociation with
dopamine neurons hypothesized to me-diate brain reward.
Marijuana produces a
distinctive behavioral syndrome that is easily distinguished from that of most
other drugs. The most prominent feature is the initial period of euphoria, or
high, which has been described as a sense of well-being and happiness. Euphoria
is fre-quently followed by a period of drowsiness or sedation. Perception of
time is altered, along with distortions in both hearing and vision. However,
illusions and halluci-nations occur infrequently. The subjective effects also
include dissociation of ideas.
The subjective effects of
marijuana vary from indi-vidual to individual as a function of dose, route of
ad-ministration, the experience and expectation of the sub-jects, and
individual vulnerability to certain psychoactive substances. Motor coordination
also may decrease, espe-cially in situations requiring highly complex motor
skills, such as flying an airplane and driving an automobile.
Increased appetite is
frequently attributed to smok-ing marijuana. Cannabinoids are effective
antiemetics, particularly in treating emesis arising during chemo-therapy. ∆9-THC has been reported to be
as effective as codeine as an analgesic, although pronounced behav-ioral
effects occur with analgesic doses.
The most consistent
pharmacological effect produced by marijuana is tachycardia, which is closely
associated with the blood levels of ∆9-THC. There is relatively lit-tle effect on
blood pressure unless large quantities of marijuana are smoked, in which case
there can be marked orthostatic hypotension. Cannabinoids are also
vasodilatory, which results in the characteristic conjunc-tival reddening
following marijuana smoking. They also reduce intraocular pressure and are
capable of produc-ing bronchodilation.
Marijuana is unique among
drugs of abuse in that there have been no credible reports of fatal overdose.
The most prominent effect of
acute marijuana use is intoxi-cation, which can impair the cognitive and motor
skills needed to complete complex tasks. Anxiety and panic reactions are
occasionally reported in inexperienced users or following use of large
quantities of marijuana. ∆9-THC causes its greatest effects on short-term mem-ory, as measured
in free-recall tasks. Marijuana does not affect the retrieval of previously
learned facts. In con-trast to alcohol, there is no residual hangover from a
single use of high quantities of marijuana.
Heavy marijuana smoking
produces bronchitis, and some individuals have evidence of precancerous lung conditions.
However, definitive evidence of the rela-tionship between marijuana smoking and
the incidence of lung cancer is lacking.
Tolerance develops to many of
∆9-THC’s effects in heavy
marijuana users. Although chronic cannabis use does not result in severe
withdrawal symptoms, numer-ous case reports attest to development of dependence
in subjects taking high doses of THC for several weeks. The most prominent
symptoms were irritability and restlessness; others included insomnia,
anorexia, in-creased sweating, and mild nausea. Cessation of mild or moderate
use of marijuana, however, does not produce a withdrawal syndrome.
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