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Chapter 11 THC Presented by Kristal Jenkins, Sherri Notestine, & Heather Risk THC Compared to Non- selective Depressants Until about 1990, marijuana was classified according to its behavioral effects, usually as a mild sedative- hypnotic agent, with effects similar to low doses of alcohol and the benzodiazepines. Unlike sedatives, however, higher doses of THC do not depress respiration and are not lethal. Little cross-tolerance occurs between THC and the sedative-hypnotics. THC also produces a unique spectrum of pharmacologic effects, including disruption in attention mechanisms, impairment of short-term memory, altered sensory awareness, analgesia, altered control of motor movements and postural control, and a possible immunosuppressive action. THC Compared to Psychedelic Drugs THC does not have a similar chemical structure to that of psychedelic drugs. Also, much less sensory disorientation than psychedelic drugs. However, although infrequent, high doses do produce hallucinations and illusions in some users. The Half-life of THC The metabolism of THC itself is quite slow: an elimination half-life of about 30 hrs. is generally accepted, although some researchers report longer half-life. Therefore, THC can persist in the body for several days to about 2 weeks. Such a delay tends to prolong and intensify the activity of subsequently smoked marijuana, forming a type of “reverse tolerance” to the drug, where the persistent low levels are potentiated by subsequently smoked THC cigarettes. Side-effects of THC Sedation altered motor coordination impaired cognition reduced short-term memory Smoking during pregnancy can cause damage to the fetus. Societal Concerns for Young Users Beginning use during early adolescence may lead to enduring effects on specific attentional functions in adulthood. Impaired ability to drive long after effects are not felt by user. Increased high-school drop out rate Increase in other problem behaviors Correlated with other educational, job, and psychosocial problems, but no causal inferences can be drawn. Increased likelihood of some form of substance abuse or dependence of other drugs. Dependence Issues Some researchers have found withdrawal symptoms of restlessness, irritability, agitation, anxiety, depression, reduced food intake, insomnia, nausea, and cramping, beginning 48 hrs. after cessation of marijuana use. However, people rarely meet the criteria for being dependent: 1. Preoccupation with the acquisition of the drug. 2. Compulsive use of the drug. 3. Relapse to or recurrent use of the drug. Cannabinoid Receptors The cannabinoid receptor is a chain of 473 amino acids with seven hydrophobic domains that extend through the cell membrane; each region is composed of one hydrophobic domain. When THC binds to its receptors, it activates G-proteins that act on various effectors including the second-messenger enzyme adenylate cyclase and both potassium and calcium ion channels. Cannabinoid Receptor Locations The hippocampus, cerebral cortex, cerebral cortex, cerebellum, and basal ganglia appear to be major loci of action of THC because these structures are involved in cognition, learning, memory, mood, and other higher intellectual functions, as well as motor functions. Treatment Marijuana, used alone, rarely results in dependence. Treatments such as psychotherapy can be appropriate for frequent users of marijuana, but this is not therapy for marijuana abuse; it is therapy for an underlying psychopathology (such as depression), one symptom of which is the use of cannabis. Therapeutic Uses THC and various derivatives such as Dronabinal (Marinol) have been used to treat nausea and vomiting associated with chemotherapy in cancer patients. Other potential uses of Dronabinal are to reduce the muscle spasms and pain of multiple sclerosis and reduce the intraocular pressure of glaucoma. Both marijuana and non-psychoactive synthetic cannabinoids effectively protect the brain from permanent injury following head trauma or stroke. Institute of Medicine’s Recommendations The Institute of Medicine concluded that cannabinoids have potential applicability for some human symptoms. They suggest that these components should be delivered by a mechanism other than inhaling smoke. Institute of Medicine’s Recommendations They also recommend: Research should continue into the physiological effects of synthetic and plant- derived cannabinoids and the natural function of cannabinoids found in the body. Clinical trials for symptom management should be conducted. Psychological effects of cannabinoids should be evaluated in clinical trials. Institute of Medicine’s Recommendations Studies to define the individual health risks of smoking marijuana should be conducted. Clinical trial of marijuana use should involve only short-term marijuana use and be conducted where there is reasonable expectations of efficacy and be approved by review boards. Short-term use of smoked marijuana should be used when all other medications have been proven to fail, symptoms can reasonably be expected to be relieved.
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