Mechanism of Action

Marijuana smokers usually inhale deeply, with the user keeping the smoke in his or her lungs for as long as possible. This allows for 25-50% of the delta-9-tetrahydrocannabinol (THC) in the marijuana cigarette to be absorbed. THC is the most potent, but by no means the only, active ingredient in marijuana. THC is the psychoactive substance of most studies, and the one that most literature agrees is responsible for its psychoactive property. THC is to marijuana as nicotine is to tobacco. The THC level in the blood is quickly distributed throughout the body, especially in areas with high fat content, such as the brain and testes for men. THC then leaches out, and small levels of the drug can be detected in the bloodsteam. This effect lasts for 2-4 days in a naive user and as long as 2 months in a heavy daily user. It should be noted that though the urine test would be positive in such a person, the marijuana would not be intoxicating, unless the person had used additional doses. As with other drugs of abuse, it is the rise in concentration of THC that is intoxicating, and this residual amount that leaches out into the bloodsteam probably does not have much effect on the user.

While the effects of the drug can be felt almost immediately, usually heralded by the giggles of the new initiator, the peak effect occurs after about 20 minutes. The user feels a mild euphoria, an alternation of sensory acuity, and a distortion of time perception. These effects gradually diminish over the next 34 hours. For persons who ingest marijuana, the effects also begin in 20-30 minutes but peak at about 2 hours. The effects of the orally ingested drug usually last for up to 8 hours. Most users of the oral form cite it as reinforcing, but describe the subjective effect as "heavy." The molecular bases of THC's actions are only now being understood. It has a number of physiological properties that act like a barbiturate, and it has anticonvulsant activity, as well as opioid properties, causing weak analgesia and antidiarrheal action. In addition, it suppresses rapid eye movement (REM) nondream sleep. Smokers of marijuana usually report an increase in nonrestorative sleep. It increases brain limbic stimulation and is thought to activate the pleasure/reward system in the brain. It is for this reason that it is an addictive agent.

In recent years, a specific receptor in the mammalian and hence the human brain has been discovered and, in fact, cloned (Sugiura & Waku, 2002). There are at least two subtypes of this receptor. Along with it, a natural ligand in marijuana, anandamide, has been identified. Substances of abuse mimic molecules that naturally occur in the brain. Such compounds (the naturally occurring ones), called ligands, have an effect on the receptors to which they have an affinity. This effect may be to stimulate, to inhibit, or a variety of in-between effects. The natural ligand for marijuana is called anandamide, and its receptor is the anandamide receptor. Interestingly, the term "anandamide" is derived from the Hindi word for bless. At present, pharmaceutical companies have synthesized both agonists and antagonists to the receptor. Much research has been conducted to identify the properties of these compounds, but it is still unclear what function they serve in mammalian and human brains. Cannabinoid receptors have been described in various regions of the brain, with the greatest abundance in the basal ganglia and hippocampus, areas involved with memory function.

The hemp plant synthesizes at least 400 chemicals, of which more than 60 are cannabinoid. Pyrolyzing the plant can create even more molecules. Very little is known about the vast majorities of these molecules or their effects on human. The most psychologically and physiologically active compound is THC. In the pyrolyzed form, it actually becomes delta-11-tetrahydrocanbonol. This molecule is believed to account for most of marijuana's effects. There are, however, numerous compounds whose effects remain completely unknown. For instance, it is known that marijuana use raises the seizure threshold overall and makes it more difficult to have a seizure (Zagnoni & Albano, 2002). THC alone decreases the seizure threshold. This property of marijuana, therefore, is not the result of THC, but rather some other cannabinoid. The two most abundant cannabinoids are cannabinol and cannabidiol. Much research is currently underway regarding the possible use of marijuana in clinical or other settings.

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