ANTI-anxiety medications are also called anxiolytics or “tranquilizing agents.”  Similar in action to the sedative-hypnotic drugs, they operate by different neural receptors and pathways. A variety of agents and drug classes provide anxiolytic effects.  […] Benzodiazepines have at least some abuse potential, although their capacity for abuse is considerably below that of other classical sedative-hypnotic agents. When these agents are abused, it is generally in a multi-drug abuse pattern.

[2a] BENZODIAZEPINES

DISCOVERED in 1959 by Leo Sternbach, working in the Roche laboratories in New York.  Dependence and Tolerance occur.  Withdrawal: rebound anxiety [65% of short-term users];  malaise, weakness, insomnia, rapid heart rate, lightheadedness, and dizziness; rarely seizures.

Xanax:

[2b] CANNABIS  / THC

The cannabis plant has been cultivated for centuries both for the production of hemp fiber and for its presumed medicinal and psychoactive properties. The smoke from burning cannabis contains many chemicals, including 61 different cannabinoids that have been identified. One of these, -9-tetrahydrocannabinol (-9-THC), produces most of the characteristic pharmacological effects of smoked marijuana.

Surveys have shown that marijuana is the most commonly used illegal drug in the United States. Usage peaked during the late 1970s, when about 60% of high school seniors reported having used marijuana, and nearly 11% reported daily use. This declined steadily among high school seniors to about 40% reporting some use during their lifetime and 2% reporting daily use in the mid- 1990s, followed by a gradual increase to 48% of 12th graders in 2002 reporting some use. Surveys among high school seniors tend to underestimate drug use because school dropouts are not surveyed. Cannabinoid receptors CB-1 (mainly CNS) and CB-2 (peripheral) have been identified and cloned. An arachidonic acid derivative has been proposed as an endogenous ligand and named anandamide. While the physiological function of these receptors and their endogenous ligands are incompletely understood, they are likely to have important functions because they are dispersed widely with high densities in the cerebral cortex, hippocampus, striatum, and cerebellum (Iversen, 2003). Specific CB-1 antagonists have been developed and are in controlled clinical trials. One of these, rimonabant, has been reported to reduce relapse in cigarette smokers and to produce weight loss in obese patients.

The pharmacological effects of -9-THC vary with the dose, route of administration, experience of the user, vulnerability [p. 623] to psychoactive effects, and setting of use. Intoxication with marijuana produces changes in mood, perception, and motivation, but the effect sought after by most users is the “high” and “mellowing out.” This effect is described as different from the stimulant high and the opiate high. The effects vary with dose, but the typical marijuana smoker experiences a high that lasts about 2 hours. During this time, there is impairment of cognitive functions, perception, reaction time, learning, and memory. Impairments of coordination and tracking behavior have been reported to persist for several hours beyond the perception of the high. These impairments have obvious implications for the operation of a motor vehicle and performance in the workplace or at school. Marijuana also produces complex behavioral changes such as giddiness and increased hunger. There are unsubstantiated claims of increased pleasure from sex and increased insight during a marijuana high. Unpleasant reactions such as panic or hallucinations and even acute psychosis may occur; several surveys indicate that 50% to 60% of marijuana users have reported at least one anxiety experience. These reactions are seen commonly with higher doses and with oral ingestion rather than smoked marijuana because smoking permits the regulation of dose according to the effects. While there is no convincing evidence that marijuana can produce a lasting schizophrenia-like syndrome, there are numerous clinical reports that marijuana use can precipitate a recurrence in people with a history of schizophrenia. One of the most controversial of the reputed effects of marijuana is the production of an “amotivational syndrome.” This syndrome is not an official diagnosis, but it has been used to describe young people who drop out of social activities and show little interest in school, work, or other goal-directed activity. When heavy marijuana use accompanies these symptoms, the drug often is cited as the cause, even though there are no data that demonstrate a causal relationship between marijuana smoking and these behavioral characteristics. conventional treatments for any of these indications (Joy et al., 1999). With the cloning of cannabinoid receptors, the discovery of endogenous ligands, and the synthesis of specific agonists and antagonists, it is likely that orally effective medications will be developed without the undesirable properties of smoked marijuana and without the deleterious effects of inhaling smoke particles and the chemical products of high-temperature combustion.

Tolerance, Dependence, and Withdrawal. Tolerance to most of the effects of marijuana can develop rapidly after only a few doses, but also disappears rapidly (Martin et al., 2004). Tolerance to large doses has been found to persist in experimental animals for long periods after cessation of drug use. Withdrawal symptoms and signs typically are not seen in clinical populations. In fact, relative to the number of marijuana smokers, few patients ever seek treatment for marijuana addiction. A withdrawal syndrome in human subjects has been described following close observation of marijuana users given regular oral doses of the agent on a research ward (Table 23–9). This syndrome, however, is only seen clinically in persons who use marijuana on a daily basis and then suddenly stop. Compulsive or regular marijuana users do not appear to be motivated by fear of withdrawal symptoms, although this has not been studied systematically. A large study of psychotherapy for self-identified marijuanadependent persons reported significant reductions in the use of marijuana after treatment, but there was no control group.

Pharmacological Interventions. Marijuana abuse and addiction have no specific treatments. Heavy users may suffer from accompanying depression and thus may respond to antidepressant medication, but this should be decided on an individual basis considering the severity of the affective symptoms after the marijuana effects have dissipated. The residual drug effects may continue for several weeks. The CB-1 receptor antagonist rimonabant has been reported to block the acute effects of smoked marijuana, but there have been no clinical trials of this medication in the treatment of marijuana dependence.

Marijuana Withdrawal Syndrome

Restlessness

Irritability

Mild agitation

Insomnia

Sleep EEG disturbance

Cannabis produces both mental and physical effects, including changes in perception, euphoria (heightened mood), and increased appetite. Short term side effects may include a decrease in short-term memory, dry mouth, impaired motor skills, red eyes, and feelings of paranoia or anxiety. Long term side effects may include addiction, decreased mental ability in those who started as teenagers, and behavioral problems in children whose mothers used cannabis during pregnancy. Onset of effects is within minutes when smoked and about 30 to 60 minutes when cooked and eaten. Effects last for between two and six hours.

The high lipid-solubility of cannabinoids results in their persisting in the body for long periods of time. Even after a single administration of THC, detectable levels of THC can be found in the body for weeks or longer (depending on the amount administered and the sensitivity of the assessment method). A number of investigators have suggested that this is an important factor in marijuana's effects, perhaps because cannabinoids may accumulate in the body, particularly in the lipid membranes of neurons.  The risk of an automobile accident while under the influence of marijuana increases to two or three times normal.

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