When smoked or vaporized, THC is absorbed via the lungs It is estimated that no more than 50% of the THC inhaled in a marijuana cigarette is actually absorbed Pharmacologic effects begin immediately In contrast, the onset of effects after oral ingestion occurs in 30 minutes to hour, and peak effects may not occur until the second and third hours after ingestion Oral ingestion of cannabis typically results in decreased bioavailability because of hepatic firstpass metabolism but more prolonged effects because of ongoing slow absorption via the GI tract The difference in kinetics of smoked versus oral cannabis has led to edible THC overdoses in users who ingest multiple doses before the first dose has begun to take effect THC readily crosses the blood–brain barrier and binds to endogenous cannabinoid receptors in the CNS and periphery Clinical Considerations The most prominent effects in humans are on the CNS and cardiovascular system In doses of up to 20 mg, THC produces effects on mood, memory, motor coordination, cognitive ability, sensorium, time sense, and self-perception There is an increased sense of well-being or euphoria accompanied by feelings of relaxation or sleepiness when subjects are alone With greater intake of THC, short-term memory is impaired, and the capacity to carry out tasks that require multiple mental steps to reach a specific goal deteriorates This effect on memory-dependent, goal-directed behavior has been called temporal disintegration and is correlated with a tendency to confuse past, present, and future Depersonalization, a sense of strangeness and unreality about one’s self, may also occur Marijuana smokers often report a voracious appetite (the “munchies”), dry mouth and throat, more vivid visual imagery, and a keener sense of hearing Altered time perception is a consistent effect of cannabinoids, so minutes seem like hours Larger doses of THC can produce frank hallucinations, delusions, and paranoid feelings Thinking becomes confused and disorganized Anxiety that reaches panic proportions may replace euphoria, often as a feeling that the drug-induced state will never end Because of the rapid onset of effects when marijuana is smoked, most users can regulate their intake to avoid the excessive doses that produce these unpleasant effects Marijuana may cause an acute exacerbation of symptoms in stabilized schizophrenics Clinical findings on examination may include tachycardia, hypertension, and marked conjunctival injection Chronic smoking of marijuana and hashish is associated with bronchitis and asthma, even though THC is a mild bronchodilator