Marijuana facts and information medical or medicinal uses, types, effects, side effects, addiction and tests zhion@zhion.com November 20, 2005 |
In the 1970s, the baby boom generation was coming of age, and its drug of choice was marijuana. By 1979, more than 60 percent of 12th-graders had tried marijuana at least once in their lives. From this peak, the percentage of 12th-graders who had ever used marijuana decreased for more than a decade, dropping to a low of 33 percent in 1992. However, in 1993, first-time marijuana use by 12th-graders was on the upswing, reaching 50 percent by 1997. Although the percentage of 12th-graders who have experience with marijuana has remained roughly level since then, there is still reason to be concerned.1 In 2002, an estimated 2.6 million Americans used marijuana for the first time. Roughly two-thirds of them were under age 18.2 Furthermore, the marijuana that is available today can be 5 times more potent than the marijuana of the 1970s. [S3] WHAT IS MARIJUANA? Marijuana - often called pot, grass, reefer, weed, herb, mary jane, or mj - is a greenish-gray mixture of the dried, shredded leaves, stems, seeds, and flowers of Cannabis sativa, the hemp plant. Most users smoke marijuana in hand-rolled cigarettes called joints, among other names; some use pipes or water pipes called bongs. Marijuana cigars called blunts have also become popular. To make blunts, users slice open cigars and replace the tobacco with marijuana, often combined with another drug, such as crack cocaine.[21] Marijuana also is used to brew tea and is sometimes mixed into foods. The major active chemical in marijuana is delta-9-tetrahydrocannabinol (THC), which causes the mind-altering effects of marijuana intoxication. The amount of THC (which is also the psychoactive ingredient in hashish) determines the potency and, therefore, the effects of marijuana. Between 1980 and 1997, the amount of THC in marijuana available in the United States rose dramatically.[22] MARIJUANA STATISTICS By combining three years of data from SAMHSA's National Survey on Drug Use and Health from 1999 to 2001, SAMHSA's Office of Applied Studies was able to produce substate estimates of substance use. In 1999 to 2001, past month use of marijuana varied from 2.3% in Northwest Iowa and 2.6% in Southern Texas to 10.3% in Boulder, Colorado and 12.2% in Boston. [S2] Of the 15 substate areas with the highest rates of past month marijuana use in the United States, five were in Massachusetts, three were in California, and two were in Colorado. [S2] A greater percentage of White youth smoke marijuana than Black youth or Hispanics. (American Indian youth have the highest rate of marijuana use of all ethnic groups.) [S1] Forty-five percent of reckless drivers not impaired by alcohol tested positive for marijuana. Illegal drugs are used by 10 to 22 percent of drivers involved in crashes.[S1] The risk of using cocaine is 104 times greater for those who have tried marijuana than for those who haven't.[S1] The average marijuana smoker spends $816 a year on his habit.[S1] Marijuana is the number one cash crop in poor areas of Kentucky, Tennessee, and West Virginia-more than 40 percent of the nationwide total.[S1] The average THC content of marijuana today is about 5 percent, more than twice the potency of the average marijuana in the sixties. It is not uncommon to find marijuana with 10 times the THC potency of twenty years ago. Hash oil can be found to have 55 percent THC content.[S1] Marijuana is the Nation's most commonly used illicit drug. More than 94 million Americans (40 percent) age 12 and older have tried marijuana at least once, according to the 2003 National Survey on Drug Use and Health (NSDUH).23 [S3] Marijuana use is widespread among adolescents and young adults. The percentage of middle-school students who reported using marijuana increased throughout the early 1990s.24 In the past few years, according to the 2004 Monitoring the Future Survey, an annual survey of drug use among the Nation's middle and high school students, illicit drug use by 8th-, 10th-, and 12th-graders has leveled off.24 Still, in 2004, 16 percent of 8th-graders reported that they had tried marijuana, and 6 percent were current users (defined as having used the drug in the 30 days preceding the survey).24 Among 10th-graders, 35 percent had tried marijuana sometime in their lives, and 16 percent were current users.24 As would be expected, rates of use among 12th-graders were higher still. Forty-six percent had tried marijuana at some time, and 20 percent were current users.24 [S3] The Drug Abuse Warning Network (DAWN), a system for monitoring the health impact of drugs, estimated that, in 2002, marijuana was a contributing factor in over 119,000 emergency department (ED) visits in the United States, with about 15 percent of the patients between the ages of 12 and 17, and almost two-thirds male.25 [S3] In 2002, the National Institute of Justice's Arrestee Drug Abuse Monitoring (ADAM) Program, which collects data on the number of adult arrestees testing positive for various drugs, found that, on average, 41 percent of adult male arrestees and 27 percent of adult female arrestees tested positive for marijuana.26 On average, 57 percent of juvenile male and 32 percent of juvenile female arrestees tested positive for marijuana. [S3] NIDA's Community Epidemiology Work Group (CEWG), a network of researchers that tracks trends in the nature and patterns of drug use in major U.S. cities, consistently reports that marijuana frequently is combined with other drugs, such as crack cocaine, PCP, formaldehyde, and codeine cough syrup, sometimes without the user being aware of it.21 Thus, the risks associated with marijuana use may be compounded by the risks of added drugs, as well. [S3] MEDICAL/MEDICINAL MARIJUANA HEALTH BENEFITS There is a legal extract of marijuana's THC for cancer sufferers. It's a pill called Merinol and requires a doctor's prescription. However, there are no studies which indicate smoking any substance is good for the lungs or health in general. In short, smoking marijuana for health benefits is a contradiction in terms.[S1] Marijuana [HU210] helps depression, research finds. Marijuana and its derivatives have been found to be good for the brain of rats.A drug (called HU210) modeled on marijuana's active ingredient increased brain cells and appeared to cut anxious, depressed behavior in rats. It is a synthetic drug that is chemically similar to marijuana's active ingredient and activates cannabinoid receptors in the brain. [A1} Researchres have shown that both embryonic and adult rat hippocampal NS/PCs are immunoreactive for CB1 cannabinoid receptors, indicating that cannabinoids could act on CB1 receptors to regulate neurogenesis. This hypothesis is supported by further findings that HU210 promotes proliferation, but not differentiation, of cultured embryonic hippocampal NS/PCs likely via a sequential activation of CB1 receptors, G(i/o) proteins, and ERK signaling. Chronic, but not acute, HU210 treatment promoted neurogenesis in the hippocampal dentate gyrus of adult rats and exerted anxiolytic- and antidepressant-like effects. X-irradiation of the hippocampus blocked both the neurogenic and behavioral effects of chronic HU210 treatment, suggesting that chronic HU210 treatment produces anxiolytic- and antidepressant-like effects likely via promotion of hippocampal neurogenesis.[A1, A4] Sativex, an experimental inhaler dispensing medical marijuana in mist form, is in its final stages of testing for marijuana. Sativex is made by GW Pharmaceuticals, UK. It may be the first prescription for a real marijuana product. [A2} Marijuana has anti-inflammatory activities, research finds Excessive inflammatory responses can emerge as a potential danger for organisms' health. Physiological balance between pro- and anti-inflammatory processes constitutes an important feature of responses against harmful events. Researchers from Germany have shown that cannabinoid receptors type 1 (CB1) mediate intrinsic protective signals that counteract proinflammatory responses. Both intrarectal infusion of 2,4-dinitrobenzene sulfonic acid (DNBS) and oral administration of dextrane sulfate sodium induced stronger inflammation in CB1-deficient mice (CB1(-/-)) than in wild-type littermates (CB1(+/+)). Treatment of wild-type mice with the specific CB1 antagonist N-(piperidino-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-pyrazole-3-carboxamide (SR141716A) mimicked the phenotype of CB1(-/-) mice, showing an acute requirement of CB1 receptors for protection from inflammation. Consistently, treatment with the cannabinoid receptor agonist R(-)-7-hydroxy-Delta(6)-tetra-hydrocannabinol-dimethylheptyl (HU210) or genetic ablation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) resulted in protection against DNBS-induced colitis. Electrophysiological recordings from circular smooth muscle cells, performed 8 hours after DNBS treatment, revealed spontaneous oscillatory action potentials in CB1(-/-) but not in CB1(+/+) colons, indicating an early CB1-mediated control of inflammation-induced irritation of smooth muscle cells. DNBS treatment increased the percentage of myenteric neurons expressing CB1 receptors, suggesting an enhancement of cannabinoid signaling during colitis. Our results indicate that the endogenous cannabinoid system represents a promising therapeutic target for the treatment of intestinal disease conditions characterized by excessive inflammatory responses. [A3] EFFECTS OF MARIJUANA IN GENERAL Marijuana can cause severe anxiety, psychotic behavior, depression, and may, in people disposed to the illness, trigger or worsen schizophrenia [S1] More teens smoke marijuana for the first time in June and July than any other time of the year. Summer's unsupervised time is the likely reason.[S1] Within 2 weeks to 3 months of quitting smoking tobacco or marijuana, lung function improves 30 percent. Within 9 months, lungs are better able to fight infection. After five years, risk of lung cancer is cut in half. After 10 years, lung cancer risk is equivalent to someone who never smoked.[S1] MARIJUANA EFFECTS ON BRAIN Scientists have learned a great deal about how THC acts in the brain to produce its many effects. When someone smokes marijuana, THC rapidly passes from the lungs into the bloodstream, which carries the chemical to organs throughout the body, including the brain. In the brain, THC connects to specific sites called cannabinoid receptors on nerve cells and thereby influences the activity of those cells. Some brain areas have many cannabinoid receptors; others have few or none. Many cannabinoid receptors are found in the parts of the brain that influence pleasure, memory, thought, concentration, sensory and time perception, and coordinated movement.27 MARIJUANA ACUTE EFFECTS When marijuana is smoked, its effects begin immediately after the drug enters the brain and last from 1 to 3 hours. If marijuana is consumed in food or drink, the short-term effects begin more slowly, usually in 1/2 to 1 hour, and last longer, for as long as 4 hours. Smoking marijuana deposits several times more THC into the blood than does eating or drinking the drug.28 Within a few minutes after inhaling marijuana smoke, an individual's heart begins beating more rapidly, the bronchial passages relax and become enlarged, and blood vessels in the eyes expand, making the eyes look red. The heart rate, normally 70 to 80 beats per minute, may increase by 20 to 50 beats per minute or, in some cases, even double.15 This effect can be greater if other drugs are taken with marijuana.29 As THC enters the brain, it causes a user to feel euphoric - or "high" - by acting in the brain's reward system, areas of the brain that respond to stimuli such as food and drink as well as most drugs of abuse. THC activates the reward system in the same way that nearly all drugs of abuse do, by stimulating brain cells to release the chemical dopamine.30,31,32 A marijuana user may experience pleasant sensations, colors and sounds may seem more intense, and time appears to pass very slowly. The user's mouth feels dry, and he or she may suddenly become very hungry and thirsty. His or her hands may tremble and grow cold. The euphoria passes after awhile, and then the user may feel sleepy or depressed. Occasionally, marijuana use produces anxiety, fear, distrust, or panic. Heavy marijuana use impairs a person's ability to form memories, recall events (see Marijuana, Memory, and the Hippocampus), and shift attention from one thing to another.8,33 THC also disrupts coordination and balance by binding to receptors in the cerebellum and basal ganglia, parts of the brain that regulate balance, posture, coordination of movement, and reaction time.11 Through its effects on the brain and body, marijuana intoxication can cause accidents. Studies show that approximately 6 to 11 percent of fatal accident victims test positive for THC. In many of these cases, alcohol is detected as well.34, 35, 36 In a study conducted by the National Highway Traffic Safety Administration, a moderate dose of marijuana alone was shown to impair driving performance; however, the effects of even a low dose of marijuana combined with alcohol were markedly greater than for either drug alone37. Driving indices measured included reaction time, visual search frequency (driver checking side streets), and the ability to perceive and/or respond to changes in the relative velocity of other vehicles. Marijuana users who have taken high doses of the drug may experience acute toxic psychosis, which includes hallucinations, delusions, and depersonalization - a loss of the sense of personal identity, or self-recognition.10,15 Although the specific causes of these symptoms remain unknown, they appear to occur more frequently when a high dose of cannabis is consumed in food or drink rather than smoked. MARIJUANA EFFECT ON HEALTH Marijuana use has been shown to increase users' difficulty in trying to quit smoking tobacco.38 This was reported in a study comparing smoking cessation in adults who smoked both marijuana and tobacco with those who smoked only tobacco. The relationship between marijuana use and continued smoking was particularly strong in those who smoked marijuana daily at the time of the initial interview, 13 years prior to the followup interview. MARIJUANA SIDE EFFECTS A study of 450 individuals found that people who smoke marijuana frequently but do not smoke tobacco have more health problems and miss more days of work than nonsmokers do.39 Many of the extra sick days used by the marijuana smokers in the study were for respiratory illnesses. [S3] Even infrequent marijuana use can cause burning and stinging of the mouth and throat, often accompanied by a heavy cough. Someone who smokes marijuana regularly may have many of the same respiratory problems that tobacco smokers do, such as daily cough and phlegm production, more frequent acute chest illnesses, a heightened risk of lung infections, and a greater tendency toward obstructed airways.4 [S3] Cancer of the respiratory tract and lungs may also be promoted by marijuana smoke.4 A study comparing 173 cancer patients and 176 healthy individuals produced strong evidence that smoking marijuana increases the likelihood of developing cancer of the head or neck, and that the more marijuana smoked, the greater the increase.17 A statistical analysis of the data suggested that marijuana smoking doubled or tripled the risk of these cancers. [S3] Marijuana has the potential to promote cancer of the lungs and other parts of the respiratory tract because it contains irritants and carcinogens.40 In fact, marijuana smoke contains 50 percent to 70 percent more carcinogenic hydrocarbons than does tobacco smoke.41 It also produces high levels of an enzyme that converts certain hydrocarbons into their carcinogenic form, levels that may accelerate the changes that ultimately produce malignant cells.42 Marijuana users usually inhale more deeply and hold their breath longer than tobacco smokers do, which increases the lungs' exposure to carcinogenic smoke. These facts suggest that, puff for puff, smoking marijuana may increase the risk of cancer more than smoking tobacco does. [S3] Some adverse health effects caused by marijuana may occur because THC impairs the immune system's ability to fight off infectious diseases and cancer. In laboratory experiments that exposed animal and human cells to THC or other marijuana ingredients, the normal disease-preventing reactions of many of the key types of immune cells were inhibited.16 In other studies, mice exposed to THC or related substances were more likely than unexposed mice to develop bacterial infections and tumors.14,43 [S3] One study has indicated that a person's risk of heart attack during the first hour after smoking marijuana is four times his or her usual risk.44 The researchers suggest that a heart attack might occur, in part, because marijuana raises blood pressure and heart rate and reduces the oxygen-carrying capacity of blood. [S3] MARIJUANA USE -EFFECTS ON SCHOOL, WORK, AND SOCIAL LIFE Students who smoke marijuana get lower grades and are less likely to graduate from high school, compared with their nonsmoking peers.20,45,46,47 [S3] Workers who smoke marijuana are more likely than their coworkers to have problems on the job. Several studies have associated workers' marijuana smoking with increased absences, tardiness, accidents, workers' compensation claims, and job turnover. A study among postal workers found that employees who tested positive for marijuana on a pre-employment urine drug test had 55 percent more industrial accidents, 85 percent more injuries, and a 75 percent increase in absenteeism compared with those who tested negative for marijuana use.48 [S3] Depression18, anxiety18, and personality disturbances50 are all associated with marijuana use. Research clearly demonstrates that marijuana use has the potential to cause problems in daily life or make a person's existing problems worse. Because marijuana compromises the ability to learn and remember information, the more a person uses marijuana the more he or she is likely to fall behind in accumulating intellectual, job, or social skills. In one study of cognition, adults were matched on the basis of their performance in the 4th grade on the Iowa Test of Basic Skills. They were evaluated on a number of cognitive measures including the 12th-grade version of the Iowa Test. Those who were heavy marijuana smokers scored significantly lower on mathematical skills and verbal expression than nonsmokers.9 [S3] Moreover, research has shown that marijuana's adverse impact on memory and learning can last for days or weeks after the acute effects of the drug wear off.9,51 For example, a study of 129 college students found that among heavy users of marijuana - those who smoked the drug at least 27 of the preceding 30 days - critical skills related to attention, memory, and learning were significantly impaired, even after they had not used the drug for at least 24 hours.33 The heavy marijuana users in the study had more trouble sustaining and shifting their attention and in registering, organizing, and using information than did the study participants who had used marijuana no more than 3 of the previous 30 days. As a result, someone who smokes marijuana once daily may be functioning at a reduced intellectual level all of the time. More recently, the same researchers showed that a group of long-term heavy marijuana users' ability to recall words from a list was impaired 1 week following cessation of marijuana use, but returned to normal by 4 weeks.51 An implication of this finding is that even after long-term heavy marijuana use, if an individual quits marijuana use, some cognitive abilities may be recovered. [S3] Another study produced additional evidence that marijuana's effects on the brain can cause cumulative deterioration of critical life skills in the long run. Researchers gave students a battery of tests measuring problem-solving and emotional skills in 8th grade and again in 12th grade.52 The results showed that the students who were already drinking alcohol plus smoking marijuana in 8th grade started off slightly behind their peers, but that the distance separating these two groups grew significantly by their senior year in high school. The analysis linked marijuana use, independently of alcohol use, to reduced capacity for self-reinforcement, a group of psychological skills that enable individuals to maintain confidence and persevere in the pursuit of goals. [S3] Marijuana users themselves report poor outcomes on a variety of measures of life satisfaction and achievement. A recent study compared current and former long-term heavy users of marijuana with a control group who reported smoking cannabis at least once in their lives, but not more than 50 times. Despite similar education and incomes in their families of origin, significant differences were found on educational attainment and income between heavy users and the control group: fewer of the cannabis users completed college and more had household incomes of less than $30,000. When asked how marijuana affected their cognitive abilities, career achievements, social lives, and physical and mental health, the overwhelming majority of heavy cannabis users reported the drug's deleterious effect on all of these measures.53 [S3] MARIJUANA USE- HEARMFUL EFFECT ON BABY DURING PREGNANCY Research has shown that some babies born to women who used marijuana during their pregnancies display altered responses to visual stimuli, increased tremulousness, and a high-pitched cry, which may indicate problems with neurological development.54, 75 During the preschool years, marijuana-exposed children have been observed to perform tasks involving sustained attention and memory more poorly than nonexposed children do.55,56 In the school years, these children are more likely to exhibit deficits in problem-solving skills, memory, and the ability to remain attentive.55,56[S3] MARIJUANA ADDICTION Marijuana can be addictive. More youth ages 12 to 17 (60 percent in 1999) enter substance abuse treatment for marijuana use than all other drug abuse combined, including alcohol.[S1] Admission for drug treatment for marijuana dependence for youth ages 12 to 17 increased 43 percent from 1994 to 1999. More than half (57 percent) of these youth had used marijuana before the age of 14.[S1] There are almost one million listings for "marijuana" on Internet search engines, but about 90 percent of them are pro-legalization or glorify marijuana use. [S1] Some cognitive deficits associated with marijuana appear to be reversible after a month of abstinence. However, those who use marijuana heavily for several years, whether they finally quit or not, tend to have markedly lower income and education levels than those who have not used it.[S1] Long-term marijuana use can lead to addiction for some people; that is, they use the drug compulsively even though it often interferes with family, school, work, and recreational activities. According to the 2003 National Survey on Drug Use and Health (NSDUH), an estimated 21.6 million Americans aged 12 or older were classified with substance dependence or abuse (9.1 percent of the total population). Of the estimated 6.9 million Americans classified with dependence on or abuse of illicit drugs, 4.2 million were dependent on or abused marijuana.57 In 2002, 15 percent of people entering drug abuse treatment programs reported that marijuana was their primary drug of abuse.58[S3] Along with craving, withdrawal symptoms can make it hard for long-term marijuana smokers to stop using the drug.49 People trying to quit report irritability, difficulty sleeping, and anxiety.59,60 They also display increased aggression on psychological tests, peaking approximately 1 week after they last used the drug.61[S3] In addition to its addictive liability, research indicates that early exposure to marijuana can increase the likelihood of a lifetime of subsequent drug problems. A recent study of over 300 fraternal and identical twin pairs, who differed on whether or not they used marijuana before the age of 17, found that those who had used marijuana early had elevated rates of other drug use and drug problems later on, compared with their twins, who did not use marijuana before age 17. This study re-emphasizes the importance of primary prevention by showing that early drug initiation is associated with increased risk of later drug problems, and it provides more evidence for why preventing marijuana experimentation during adolescence could have an impact on preventing addiction.62[S3] MARIJUANA TREATMENTS Treatment programs directed solely at marijuana abuse are rare, partly because many who use marijuana do so in combination with other drugs, such as cocaine and alcohol. However, with more people seeking help to control marijuana abuse, research has focused on ways to overcome problems with abuse of this drug.63[S3] One study of adult marijuana users found comparable benefits from a 14-session cognitive-behavioral group treatment and a 2-session individual treatment that included motivational interviewing and advice on ways to reduce marijuana use.64 Participants were mostly men in their early thirties who had smoked marijuana daily for over 10 years. By increasing patients' awareness of what triggers their marijuana use, both treatments sought to help them devise avoidance strategies. Use, dependence symptoms, and psychosocial problems decreased for at least 1 year after both treatments. About 30 percent of users were abstinent during the last 3-month followup period. Another study suggests that giving patients vouchers for abstaining from marijuana can improve outcomes.65 Vouchers can be redeemed for such goods as movie passes, sports equipment, or vocational training.[S3] No medications are now available to treat marijuana abuse. However, recent discoveries about the workings of THC receptors have raised the possibility that scientists may eventually develop a medication that will block THC's intoxicating effects. Such a medication might be used to prevent relapse to marijuana abuse by reducing or eliminating its appeal.[S3] MARIJUANA TEST Most THC/marijuana drug tests are based on the prinicple of the highly specific immunochemical reactions between antigens and antibodies, which are used for the analysis of specific substances in biological fluids. The senstivity is usualy 50 ng/ml of THC. The peak effect of smoking marijuana occurs in 20-30 minutes and the duration is 90-120 minutes after one cigarette. Elevated urinary metabolite levels are found within hours of exposure and remain detectable for 3-20 days after smoking. Currently, there are also saliva drug test kits for marijuana (THC). GLOSSARY Addiction: A chronic, relapsing disease characterized by compulsive drug-seeking and abuse and by long-lasting chemical changes in the brain. Cannabinoids: Chemicals that help control mental and physical processes when produced naturally by the body and that produce intoxication and other effects when absorbed from marijuana. Carcinogen: Any substance that causes cancer. Dopamine: A brain chemical, classified as a neurotransmitter, found in regions of the brain that regulate movement, emotion, motivation, and pleasure. Hippocampus: An area of the brain crucial for learning and memory. Hydrocarbon: Any chemical compound containing only hydrogen and carbon. Psychoactive: Having a specific effect on the mind. THC: Delta-9-tetrahydrocannabinol; the main active ingredient in marijuana, which acts on the brain to produce its effects. Withdrawal: Symptoms that occur after use of a drug is reduced or stopped. QUESTION: HOW LONG DOES MARIJUANA STAY IN OUR BODY? Pharmacokinetics of cannabinoids.Pain Res Manag. 2005 Autumn;10(A):15A-22A. McGilveray IJ., McGilveray Pharmacon Inc, Ottawa, Canada. Delta-9-tetrahydrocannabinol (Delta-9-THC) is the main psychoactive ingredient of cannabis (marijuana). The present review focuses on the pharmacokinetics of THC, but also includes known information for cannabinol and cannabidiol, as well as the synthetic marketed cannabinoids, dronabinol (synthetic THC) and nabilone. The variability of THC in plant material (0.3% to 30%) leads to variability in tissue THC levels from smoking, which is, in itself, a highly individual process. THC bioavailability averages 30%. With a 3.55% THC cigarette, a peak plasma level of 152∓86.3 ng/mL occured approximately 10 min after inhalation. Oral THC, on the other hand, is only 4% to 12% bioavailable and absorption is highly variable. THC is eliminated from plasma in a multiphasic manner, with low amounts detectable for over one week after dosing. A major active 11-hydroxy metabolite is formed after both inhalation and oral dosing (20% and 100% of parent, respectively). THC is widely distributed, particularly to fatty tissues, but less than 1% of an administered dose reaches the brain, while the spleen and body fat are long-term storage sites. The elimination of THC and its many metabolites (from all routes) occurs via the feces and urine. Metabolites persist in the urine and feces for several weeks. Nabilone is well absorbed and the pharmacokinetics, although variable, appear to be linear from oral doses of 1 mg to 4 mg (these doses show a plasma elimination half-life of approximately 2 h). As with THC, there is a high first-pass effect, and the feces to urine ratio of excretion is similar to other cannabinoids. Pharmacokinetic-pharmacodynamic modelling with plasma THC versus cardiac and psychotropic effects show that after equilibrium is reached, the intensity of effect is proportional to the plasma THC profile. Clinical trials have found that nabilone produces less tachycardia and less euphoria than THC for a similar antiemetic response. Assay of plasma cannabidiol by capillary gas chromatography/ion trap mass spectroscopy following high-dose repeated daily oral administration in humans.Pharmacol Biochem Behav. 1991 Nov;40(3):517-22. Consroe P, Kennedy K, Schram K.College of Pharmacy, University of Arizona Health Sciences Center, Tucson 85721. Plasma levels of cannabidiol (CBD) were ascertained weekly in 14 Huntington's disease patients undergoing a double-blind, placebo-controlled, crossover trial of oral CBD (10 mg/kg/day = about 700 mg/day) for 6 weeks. The assay procedure involved trimethylsilyl (TMS) derivatization of CBD and the internal standard delta-6-tetrahydrocannabinol (THC), capillary column gas chromatography, ion trap mass spectroscopy in positive ion chemical ionization mode using isobutane, and calculations of CBD levels based on peak ion intensity of the 387 M + H peak of delta-6-THC-TMS and the 459 M + H peak of CBD-2TMS. The sensitivity of the assay was about 500 pg/ml, and the precision was about 10-15%. Mean plasma levels of CBD ranged from 5.9-11.2 ng/ml over the 6 weeks of CBD administration. CBD levels averaged 1.5 ng/ml one week after CBD was discontinued, and were virtually undetectable thereafter. The elimination half-life of CBD was estimated to be about 2-5 days, and there were no differences between genders for half-life or CBD levels. Additionally, no plasma delta-1-THC, the major psychoactive cannabinoid of marijuana, was detected in any subject. Human urinary excretion profile after smoking and oral administration of [14C]delta 1-tetrahydrocannabinol.J Anal Toxicol. 1990 May-Jun;14(3):176-80. Johansson E, Gillespie HK, Halldin MM. Department of Pharmacognosy, BMC, Uppsala, Sweden. The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of [14C]delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of 14C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of 14C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively. Urinary excretion half-life of delta 1-tetrahydrocannabinol-7-oic acid in heavy marijuana users after smoking.J Anal Toxicol. 1989 Jul-Aug;13(4):218-23. Johansson E, Halldin MM. Department of Pharmacognosy, Uppsala, Sweden. The urinary excretion of the total amount of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites, with special emphasis on delta 1-tetrahydrocannabinol-7-oic acid (delta 1-THC-7-oic acid), was studied in thirteen heavy Cannabis users after smoking administration of delta 1-THC, followed by a four week discontinuation period. The total amount of delta 1-THC metabolites and the levels of delta 1-THC-7-oic acid could be followed up to 25 days after abstinence using EMIT d.a.u. cannabinoid assay and high-performance liquid chromatography (HPLC). The urinary excretion half-life, calculated from the concentrations of delta 1-THC-7-oic acid versus time, ranged from 0.8-9.8 days with a mean (+/- SD) of 3.0 +/- 2.3 days. Most of the delta 1-THC-7-oic acid was excreted as conjugate and only trace amounts of unconjugated delta 1-THC-7-oic acid were detected. The total concentrations of delta 1-THC-7-oic acid in urine were compared to the concentrations of "cross-reacting cannabinoids", within the linear range of 20-75 ng/mL, obtained in the semiquantitative EMIT d.a.u. cannabinoid assay. The average ratio of "EMIT concentrations"/delta 1-THC-7-oic acid concentrations obtained by HPLC analysis was 1.23 +/- 84% (C.V.) for 78 urine samples. A total of 83% of the samples with positive EMIT levels (cutoff 20 ng/mL) was confirmed by HPLC analysis (cutoff 7 ng/mL). Terminal elimination plasma half-life of delta 1-tetrahydrocannabinol (delta 1-THC) in heavy users of marijuana. Eur J Clin Pharmacol. 1989;37(3):273-7. Johansson E, Halldin MM, Agurell S, Hollister LE, Gillespie HK. Department of Pharmacognosy, Uppsala University, Sweden. The terminal elimination half-life of delta 1-tetrahydrocannabinol (delta 1-THC) was investigated in eight men who were heavy users of marijuana. A stable isotope assay, following smoking deuterium-labeled delta 1-THC, was used to determine plasma concentrations. In two additional users plasma levels were followed after administration of unlabeled delta 1-THC. The subjects were asked to smoke a "loading dose" of 56 mg delta 1-THC during two days and then abstain from all marijuana use for 4 weeks. The pharmacokinetic behavior was consistent with a multicompartment model with a mean plasma elimination half-life of delta 1-THC of 4.3 days when concentrations were followed for 10-15 days after smoking. In the two subjects with detectable plasma levels during 4 weeks, half-lives of 9.6 and 12.6 days was obtained. THIS ARTICLE IS FOR YOUR REFERNCE ONLY. IF YOU HAVE ANY QUESTIONS, PLEASE, CONSULT WITH YOUR DOCTOR. DO NOT COPY NOR TRANSFER THIS ARTICLE TO OTHER WEB-SITES. 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