HairConfirm

Confidential Forensic Drug of Abuse Hair Testing

Anonymous, Quantitative and *Historical Forensic Drug of Abuse Laboratory Testing using a Hair Sample. U.S. FDA cleared. Home Version Frequently asked Questions.

Now Features Improved Reporting!

48 hour Laboratory Processing Online Sample Tracking Detailed quantitative Laboratory Analysis in pg/gm with Drug user type (low, medium, high) Online Laboratory Report can be downloaded and printed.

MARIJUANA COCAINE CRACK COCAINE OPIATES METHAMPHETAMINES ECSTASY PCP AMPHETAMINES

The HairConfirm personal forensic hair analysis drug of abuse testing service is the only at home drug testing kit that providesa *history (up to several months) of current or previous drug usefor the five most abused illicit drugs and drug categories: Methamphetamines including Ecstasy , Marijuana, Opiates, Cocaine and Phencyclidines (PCP) without the need for urine specimen collection. The only sample required is a small lock of the test subject's hair (approximately the size of a shoelace tip) taken at the scalp line. Confidential and non-invasive, The HairConfirm drug test provides a qualitative determination of past drug use over a period of approximately three (3) months using forensic laboratory analysis. Online Sample tracking and report download direct from the Laboratory. The HairConfirm hair test is FDA cleared for professional and personal home use.

* Historical determination of identified drug use is dependent upon several important characteristics of the hair sample submitted including but not limited to length (average growth rate of .5"/month for scalp hair), and proximity to the hairline (closest to hair root). Details of sample characteristics and requirements are discussed in the instruction manual included with this kit.

INTENDED USE: The HairConfirm forensic drug test is a forensic, quantitative, anonymous laboratory analysis for the presence of illicit drug metabolites in the core structure of human hair shafts. The HairConfirm kit is a forensic drug of abuse hair testing service cleared by the U.S. FDA. Testing is completely anonymous. Each HairConfirm kit contains a special key code and password number which is the only information required to obtain the laboratory test results using either the online laboratory tracking service or the toll free number provided. Furthermore, test confidentiality is 100% guaranteed. No names or other personal identity information is used during the testing process, only the special code number test key. The HairConfirm

personal forensic laboratory analysis for drugs of abuse also provides a quantitative laboratory report that can be downloaded and printed directly online using the special code and password key provided with each test kit. Additionally a toll free number call in service for test results and counseling referrals is provided. Test results indicate a negative or positive for each class of abused drugs tested for with quantitative readings expressed in pica grams per milligram for positive results. Results are generally available online within 2 business days after receipt of sample by the testing laboratory. Under certain circumstances, it may desirable to obtain a historical record of drug use. In-vitro urine and saliva drug test detection rates are limited to the metabolic half life of drugs while in the body's system. Sufficient abstinence prior to a drug test can therefore produce a negative test result when in fact the individual has a history of drug abuse. Institutions and employers may want this information particularly in critical or sensitive occupations. The HairConfirm forensic drug testing service provides the same clinical results that can be obtained from a local medical or forensic laboratory, and the test is FDA cleared for consumer use, without the requirement of a physician's order and resultant potential invasion of privacy. All that is required for testing are strains of hair in an amount approximate to the diameter of a shoelace tip (40-50 strands). Sample hair is usually obtained by cutting a lock from the back of the head at the root line. Detection of historical drug use is dependent on the length of the hair sample from the root line. The average growth rate of hair is one-half inch per month. Therefore an approximate 90 day history of drug use would require a minimum of one and one-half inches of hair length measured from the root line. PRINCIPLE

The presence of drugs in hair is based on a simple principle. Drugs which are ingested into the body circulate in a person's bloodstream which nourishes developing hair follicles. As a result, trace amounts of the target drug or drug metabolite are deposited in the hair follicle andbecome entrapped in the core of the hair shaft as it grows out from the hair follicle. Normal growth rates for human hair are approximately one-half inch per month. By testing for the presence of drugs in the hair shaft core on a given length of hair, a historical record can be achieved on past drug usage based on the length of the hair sample submitted measured from the scalp line. For example; if a 1.5" length hair sample measured from the scalp line is submitted, and knowing that on average head hair grows at the rate of .5" inch per month, then it can be assumed that a positive test result would imply that a drug was consumed sometime in the past 3 month period. Since target drug or drug metabolite residues are chemically and structurally stable for an extended period of time within the hair shaft core, they cannot be externally washed, bleached, chemically treated or flushed out of the hair structure. Consequently there is little possibility of sample contamination or manipulation. For this reason many courts and legal entities have chosen a forensic hair drug test as the preferred method of drug testing. Gas

chromatography/mass spectrometry (GC/MS) forensic laboratory analysis of the hair shaft from an individual can achieve highly accurate drug test results and provide a historical use record. Generally it takes approximately 5 days for drugs to show up in a person's hair and will continue to be detectable in new hair growth for several months. Most questions about the HairConfirm Test are answered here: Frequently Asked Questions (FAQ) TEST PROCEDURE AND REPORTING The HairConfirm forensic drug screening test is very easy to perform privately and confidentially. All that is required is obtaining a sample of hair according to test instructions and returning the completed sample packet to the laboratory for processing using the postage paid return method (US First class mail: Standard and Standard Plus Prescription Drug Test Versions) or FEDEX Priority Overnight (Express Test Version US Customers Only). Generally, results of the test are available within 2 business days after receipt by the laboratory (dependent on laboratory workload and scheduling) and are obtained online using the assigned unique test key code and user passcode included with each test kit. The completed laboratory report can be downloaded and printed directly online from the Laboratory. Results may also be obtained verbally using the toll free number provided.

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Seal and Label Sample. Affix unique Sample ID# Code Label Provided

Return to Lab Postage Paid Envelope (Standard Versions) Prepaid FEDEX Overnight (Express Version)
US Customers Only

Register Sample ID# and passcode Online with the Laboratory

Track Test Result Progress Online and Download Test Result Laboratory Report

Print Laboratory Test Result View Sample

HairConfirm Test Frequently Asked Questions (FAQ) AVAILABILITY

Three Versions of the HairConfirm forensic drug testing service are available, the Standard Version, the Standard Plus Prescription Drugs Version and the Express Version (see the chart below). All kits are the same with regard to sample collection and laboratory processing time. The Standard and Standard Plus Prescription Drugs versions of the test includes a prepaid first class US Postal envelope for sample return. The Express Version of the test includes a prepaid FEDEX Overnight mailer (US Customers Only). Test Processing time of 2 business days after laboratory sample receipt is the same for all test versions. Only the sample return time to the laboratory is expedited with the Express Version (US Customers Only) . Export customers should choose the Standard Versions of the Kits as International FEDEX return service for samples is not supported.

Version Drugs Tested

HairConfirm STAN DARD Marijuana, Cocaine, Crack Cocaine, Opiates, Methamphetamines, PCP, Ecstasy, Amphetamines.

HairConfirm STANDAR D PLUS PRESCRIPTION Marijuana, Cocaine, Crack Cocaine, Opiates, Methamphetamines, PCP, Ecstasy, Amphetamines PLUSPres cription Drugs Hydrocodone (Vicodin, Lortab, Lorcet) Oxycodone (Oxycotin, Percocet, Percodan) Hydromorphone (Dilaudid)

HairConfirm EXP RESS Marijuana, Cocaine, Crack Cocaine, Opiates, Methamphetamines , PCP, Ecstasy, Amphetamines.

Return Method

Prepaid USPS First Prepaid USPS First Class Class Envelope Envelope Sample Return Mailer Sample Return Mailer 48 hours receipt by laboratory 48 hours receipt by laboratory Online. Download and Printed Report. View Sample Report

Prepaid FEDEX Overnight Mailer (U.S. Customers Only) 48 hours receipt by laboratory Online. Download and Printed Report. View Sample Report

Processi ng Time

Reportin Online. Download g* and Printed Report. View Sample Report

Each HairConfirm forensic drug testing service test kit is all inclusive with all the components and materials required to perform one drug screening forensic laboratory analysis for the presence and past use (up to several months) of the most abused drugs and drug categories as outlined above. Comprehensive test instructions are included detailing the sample collection, submission and reporting process. Also a Q&A or FAQ section is provided and a toll free 800 support number is included. There are no additional costs beyond the kit purchase price and all laboratory processing fees and mailing costs are prepaid and included. Professional and reseller volume discounts may apply to quantity purchases beyond the sale units listed. Contact Customer Service for volume quotations for quantities exceeding 24 units of each test version. Most questions about the HairConfirm Test are answered here: Frequently Asked Questions (FAQ) Description HairConfirm STANDARD Forensic Laboratory Drug Testing Service Packaging Boxed Collection Kit Units One (1) Kit Three (3) Kits Six (6) Kits Twelve (12) Kits HairConfirm STANDARD PLUS PRESCRIPTION Forensic Laboratory Drug Testing Service Collection Kit One (1) Kit Three (3) Kits Six (6) Kits Twelve (12) Kits **HairConfirm EXPRESS Forensic Laboratory Drug Testing Service Boxed Collection Kit One (1) Kit Three (3) Kits Six (6) Kits Cost $75.00 $210.00 $360.00 $675.00 $95.00 $270.00 $480.00 $900.00 $89.00 $249.00 $450.00

Twelve (12) Kits $790.00 * Laboratory processing time is generally 48 hours ( except weekends) after Laboratory receipt and may vary depending on scheduling ** Export Customers should order the Standard Test Versions only as International FEDEX sample return service is not provided If the order buttons are absent or inoperable, please use the pricing overview page to order.

Medical cannabis
From Wikipedia, the free encyclopedia

American Cannabis Indica purchased at a Medical Cannabis dispensary.

Cannabis Indica fluid extract, American Druggists Syndicate, pre-1937.

Medical cannabis refers to the use of parts of the herb cannabis (also referred to asmedical marijuana) as a physician-recommended form of medicine or herbal therapy, or to synthetic forms of specific cannabinoids such as THC as a physician-recommended form of medicine. The Cannabis plant from which the cannabis drug is derived has a long history of medicinal use, with evidence dating back to 2,737 BCE.[1] Synthetic cannabinoids, such asMarinol and Cesamet, are

available as prescription drugs in some countries. A number of studies, some disputed, claim that medical cannabis relieves symptoms and is helpful in the treatment of many diseases.
Contents
[hide]

o o o o o o o o o o o o o o o o o o o o

1 Use 2 Clinical applications 3 Recent studies 3.1 Safety of cannabis 3.2 Alzheimer's disease 3.3 Mental disorders 3.4 Lung cancer and chronic obstructive pulmonary disease 3.5 Breast cancer 3.6 HIV/AIDS 3.7 Brain cancer 3.8 Opioid dependence 3.9 Controlling ALS symptoms 3.10 Spasticity in multiple sclerosis 3.11 Treatment of inflammatory skin disease 4 Medicinal compounds 4.1 Tetrahydrocannabinol 4.2 Cannabidiol 4.3 Cannabinol 4.4 -Caryophyllene 4.5 Cannabigerol 5 Pharmacologic THC and THC derivatives 6 Criticism 7 Harm reduction 8 Organizational positions 9 History 9.1 Ancient China and Taiwan 9.2 Ancient Egypt 9.3 Ancient India 9.4 Ancient Greece

o o o o o o o o

9.5 South East Asia 9.6 Medieval Islamic world 10 Modern history 11 National and international regulations 11.1 Austria 11.2 Canada 11.3 Germany 11.4 Spain 11.5 United Kingdom 11.6 United States 12 See also 13 References 14 Further reading 15 External links

[edit]Use
The medicinal value of cannabis is controversial. A large majority of national governments do not recognize the use of plant parts from the plant Cannabis Sativa as something that doctors can recommend to their patients. A number of these governments, including the U.S. Federal Government, allow treatment with one or more specific synthetic cannabinoids for one or more disorders. Supporters of medical cannabis argue that cannabis does have several well-documented beneficial effects.[2][3][4][5] Among these are: the amelioration of nausea and vomiting, stimulation of hunger in chemotherapy and AIDS patients, lowered intraocular eye pressure (shown to be effective for treating glaucoma), as well as gastrointestinal illness. Its effectiveness as an analgesic has been suggestedand disputedas well. There are several methods for administration of dosage, including vaporizing or smoking dried buds, drinking, or eating extracts, and taking capsules. The comparable efficacy of these methods was the subject of an investigative study[5] conducted by the National Institutes of Health. Synthetic cannabinoids are available as prescription drugs in some countries. Examples are Marinol (The United States and Canada) and Cesamet (Canada, Mexico, the United Kingdom, and the United States). While utilizing cannabis for recreational purposes is illegal in many parts of the world, many countries are beginning to entertain varying levels of decriminalization for medical usage, including Canada,

Austria, Germany, the Netherlands, Spain, Israel, Italy, Finland, and Portugal. In the United States, federal law outlaws all use of herb parts from Cannabis, while some states have approved use of herb parts from Cannabis as medical cannabis in conflict with federal law. The United States Supreme Court has ruled in United States v. Oakland Cannabis Buyers' Coop and Gonzales v. Raich that the federal government has a right to regulate and criminalize cannabis, even for medical purposes. A person can therefore be prosecuted for a cannabis-related crime even if it is medical cannabis that is legal according to the laws of this state.

[edit]Clinical

applications

"Victoria", the United States' first legal medical marijuana plant grown by The Wo/Men's Alliance for Medical Marijuana.[citation needed]

A 2002 review of medical literature by Franjo Grotenhermen states that medical cannabis has established effects in the treatment of nausea, vomiting, premenstrual syndrome, unintentional weight loss, insomnia, and lack of appetite. Other "relatively well-confirmed" effects were in the treatment of "spasticity, painful conditions, especially neurogenic pain,movement disorders, asthma, [and] glaucoma".[6] Preliminary findings indicate that cannabis-based drugs could prove useful in treatinginflammatory bowel disease, migraines, fibromyalgia, and related conditions.[7] Medical cannabis has also been found to relieve certain symptoms of multiple sclerosis[8]and spinal cord injuries[9][10][11] by exhibiting antispasmodic and muscle-relaxant properties as well as stimulating appetite. Other studies state that cannabis or cannabinoids may be useful in treating alcohol abuse,
[12]

amyotrophic lateral sclerosis,[13][14] collagen-induced arthritis,[15] asthma,[16]atherosclerosis,[17] bipolar

disorder,[18][19] colorectal cancer,[20] HIV-Associated Sensory Neuropathy[21] depression,[22][23][24]

[25] [34]

dystonia,[26] epilepsy,[27][28][29] digestive diseases,[30] gliomas,[31][32] hepatitis C,[33] Huntington's disease, leukemia,[35] skin tumors,[36] methicillin-resistant Staphylococcus aureus (MRSA),[37] Parkinson's

disease,[38] pruritus,[39][40] posttraumatic stress disorder (PTSD),[41] psoriasis,[42] sickle-cell disease,

[43]

sleep apnea,[44] and anorexia nervosa.[45] Controlled research on treatingTourette syndrome with a

synthetic version of tetrahydrocannabinol, (brand name Marinol) (the main psychoactive chemical found in cannabis), showed the patients taking Marinol had a beneficial response without serious adverse effects;[46][47] other studies have shown that cannabis "has no effects on tics and increases the individuals inner tension".[48] Case reports found that marijuana helped reduce tics, but validation of these results requires longer, controlled studies on larger samples.[49][50]

[edit]Recent [edit]Safety

studies

of cannabis

According to an approved statement from the US Department of Justice in 1988, "Nearly all medicines have toxic, potentially lethal effects. But marijuana is not such a substance. There is no record in the extensive medical literature describing a proven, documented cannabis-induced fatality. In practical terms, marijuana cannot induce a lethal response as a result of drug-related toxicity."[51] From January 1997 to June 2005, the U.S. Food and Drug Administration (FDA) reported zero deaths caused by the primary use of marijuana. Through that time period, 279 deaths were reported where marijuana was a possible "concomitant" drug used in conjunction with other drugs at the time of death. In contrast, common FDA-approved drugs which are often prescribed in lieu of marijuana (such asantiemetics and anti-psychotics), were the primary cause of 10,008 deaths.[52]

[edit]Alzheimer's

disease

Research done by the Scripps Research Institute in California shows that the active ingredient in marijuana, THC, prevents the formation of deposits in the brain associated with Alzheimer's disease. THC was found to prevent an enzyme called acetylcholinesterase from accelerating the formation of "Alzheimer plaques" in the brain more effectively than commercially marketed drugs. THC is also more effective at blocking clumps of protein that can inhibit memory and cognition in Alzheimers patients, as reported in Molecular Pharmaceutics.[53]

[edit]Mental

disorders

There has been evidence that smoking marijuana can have a positive effect on disorders such as Schizophrenia, bipolar disorder, or depression.[citation needed] In patients with bipolar disorder subjects have been shown to actually become better after smoking marijuana increasing the rate at which these patients go from high to low.[citation needed] In the case of depression many users have reported that their moods have become better.[citation needed] Research done on lab rats and animals has shown that marijuana can act as an anti-depressant but in other studies done on humans this is not the case, actually pushing the subjects further into their depression.[citation needed] A study of 50,000 Swedish soldiers who had smoked at least once were twice as likely to develop schizophrenia as those who

had not smoked. The study concluded that either smoking caused a higher rate of schizophrenia, or that schizophrenics were more likely to be drawn to marijuana.[54] A study by Keele University commissioned by the British government found that between 1996 and 2005 there had been significant reductions in the incidence and prevalence of schizophrenia. From 2000 onwards there were also significant reductions in the prevalence of psychoses. The authors say this data is "not consistent with the hypothesis that increasing cannabis use in earlier decades is associated with increasing schizophrenia or psychoses from the mid-1990s onwards".[55] A 10 year study on 1923 individuals from the general population in Germany, aged 1424, concluded that cannabis use is a risk factor for the development of incident psychotic symptoms. Continued cannabis use might increase the risk for psychotic disorder.[56]

[edit]Lung

cancer and chronic obstructive pulmonary disease

The evidence to date is conflicting as to whether smoking cannabis increases the risk of developing lung cancer or chronic obstructive pulmonary disease (COPD) among people who do not smoke tobacco. In 2006 a study by Hashibe, Morgenstern, Cui, Tashkin, et al.suggested that smoking cannabis does not, by itself, increase the risk of lung cancer. Several subsequent studies have found results suggesting the reverse, however many of these were not completed with proper scientific controls and have subsequently been discredited. Many studies did report a strongly synergistic effect, however, between tobacco use and smoking cannabis such that tobacco smokers who also smoked cannabis dramatically increased their already very high risk of developing lung cancer or chronic obstructive pulmonary disease by as much as 300%. Some of these research results follow below:

In 2006, Hashibe, Morgenstern, Cui, Tashkin, et al. presented the results from a study

involving 2,240 subjects that showed non-tobacco users who smoked marijuana did not exhibit an increased incidence of lung cancer or head-and-neck malignancies. These results were supported even among very long-term, very heavy users of marijuana.[57] Tashkin, a pulmonologist who has studied marijuana for 30 years, said, "It's possible that tetrahydrocannabinol (THC) in marijuana smoke may encourage apoptosis, or programmed cell death, causing cells to die off before they have a chance to undergo malignant transformation". He further commented that "We hypothesized that there would be a positive association between marijuana use and lung cancer, and that the association would be more positive with heavier use. What we found instead was no association at all, and even a suggestion of some protective effect."[unreliable medical source?][58][unreliable medical source?][59]

A case-control study of lung cancer in adults 55 years of age and younger found that

the risk of lung cancer increased 8% (95% confidence interval (CI) 215) for each joint-year of cannabis smoking, after adjustment for confounding variables including cigarette smoking, and 7% (95% CI 59) for each pack-year of cigarette smoking, after adjustment for confounding variables including cannabis smoking.[60]

A 2008 study by Hii, Tam, Thompson, and Naughton found that marijuana smoking

leads to asymmetrical bullous disease, often in the setting of normal CXR and lung function. In subjects who smoke marijuana, these pathological changes occur at a younger age (approximately 20 years earlier) than in tobacco smokers.[61]

Researchers from the University of British Columbia presented a study at the

American Thoracic Society 2007 International Conference showing that smoking marijuana and tobacco together more than tripled the risk of developing COPD over just smoking tobacco alone.[unreliable medical source?][62] Similar findings were released in April 2009 by the Vancouver Burden of Obstructive Lung Disease Research Group. The study reported that smoking both tobacco and marijuana synergistically increased the risk of respiratory symptoms and COPD. Smoking only marijuana, however, was not associated with an increased risk of respiratory symptoms of COPD.[unreliable medical source?][63][64] In a related commentary, pulmonary researcher Donald Tashkin wrote, "...we can be close to concluding that marijuana smoking by itself does not lead to COPD".[65]

[edit]Breast
A

cancer

According to a 2007 study at the California Pacific Medical Center Research Institute, cannabidiol (CBD) may stop breast cancer from spreading throughout the body.[66] These researchers believe their discovery may provide a non-toxic alternative to chemotherapy while achieving the same results minus the painful and unpleasant side effects. The research team says that CBD works by blocking the activity of a gene called Id-1, which is believed to be responsible for a process called metastasis, which is the aggressive spread of cancer cells away from the original tumor site.[66]
[edit]HIV/AIDS

Investigators at Columbia University published clinical trial data in 2007 showing that HIV/AIDS patients who inhaled cannabis four times daily experienced substantial increases in food intake with little evidence of discomfort and no impairment of cognitive performance. They concluded that smoked marijuana has a clear medical benefit in HIV-positive patients.[67][68] In another study in 2008, researchers at theUniversity of California, San Diego School of Medicine found that marijuana significantly reduces HIV-related neuropathic pain when added to a patient's already-prescribed pain management regimen and may be an "effective option for pain relief" in those whose pain is not controlled with current medications. Mood disturbance, physical disability, and quality of life all improved significantly during study treatment.[69] Despite management with opioids and other pain modifying therapies, neuropathic pain continues to reduce the quality of life and daily functioning in HIV-infected individuals. Cannabinoid receptors in the central and peripheral nervous systems have been shown to modulate pain perception. No serious adverse effects were reported, according to the study published by the American Academy of Neurology.[70] A study examining the effectiveness of different drugs for HIV associated neuropathic pain found that smokedCannabis was one of only three drugs that showed evidence of efficacy.[71]
[edit]Brain

cancer

A study by Complutense University of Madrid found the chemicals in marijuana promotes the death of brain cancer cells by essentially helping them feed upon themselves in a process called autophagy. The research team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and in people with brain tumors. When mice with the human brain cancer cells received the THC, the tumor shrank. Using electron microscopes to analyze brain tissue taken both before and after a 26to 30-day THC treatment regimen, the researchers found that THC eliminated cancer cells while leaving healthy cells intact.[72] The patients did not have any toxic effects from the treatment; previous studies of THC for the treatment of cancer have also found the

therapy to be well tolerated. However, the mechanisms which promote THC's tumor cellkilling action are unknown.[72]
[edit]Opioid

dependence

Injections of THC eliminate dependence on opiates in stressed rats, according to a research team at the Laboratory for Physiopathology of Diseases of the Central Nervous System (France) in the journal Neuropsychopharmacology.[73] Deprived of their mothers at birth, rats become hypersensitive to the rewarding effect of morphine and heroin (substances belonging to the opiate family), and rapidly become dependent. When these rats were administered THC, they no longer developed typical morphine-dependent behavior. In the striatum, a region of the brain involved in drug dependence, the production of endogenous enkephalins was restored under THC, whereas it diminished in rats stressed from birth which had not received THC. Researchers believe the findings could lead to therapeutic alternatives to existing substitution treatments.[73] In humans, drug treatment subjects who use cannabis intermittently are found to be more likely to adhere to treatment for opioid dependence.[74] Historically, similar findings were reported by Edward Birch, who, in 1889, reported success in treating opiate and chloral addiction with cannabis.[75]
[edit]Controlling

ALS symptoms

Recent research has been conducted on if the use of marijuana could control some of the symptoms of ALS or Lou Gehrig Disease. A survey was conducted on 131 people who suffered from ALS. The survey asked if the subjects had used marijuana in the last 12 months to control some of their symptoms. The survey resulted in 13 people who had used the drug in some form to control symptoms. The subjects all concluded that the symptoms of appetite loss, depression, pain, spasticity, drooling, and weakness.[76]
[edit]Spasticity

in multiple sclerosis

A review of six randomized controlled trials of a combination of THC and CBD extracts for the treatment of MS related muscle spasticity reported, "Although there was variation in the outcome

measures reported in these studies, a trend of reduced spasticity in treated patients was noted." The authors postulated that "cannabinoids may provide neuroprotective and anti-inflammatory benefits in MS."[77] A small study done on whether or not marijuana could be used to control tremors of MS patients was conducted. The study found that there was no noticeable difference of the tremors in the patients. Although there was no difference in the tremors the patients felt as if their symptoms had lessened and their quality of life had improved. The researchers concluded that the mood enhancing or cognitive effects that cannabis has on the brain could have given the patients the effect that their tremors were getting better.[76]
[edit]Treatment

of inflammatory skin disease

The abundant distribution of cannabinoid receptors on skin nerve fibers and mast cells provides implications for an anti-inflammatory, anti-nociceptive action of cannabinoid receptor agonists and suggests their putatively broad therapeutic potential[78]
[edit]Medicinal

compounds

Cannabis contains over 300 compounds. At least 66 of these are cannabinoids,[79][80] which are the basis for medical and scientific use of cannabis. This presents the research problem of isolating the effect of specific compounds and taking account of the interaction of these compounds.[81] Cannabinoids can serve as appetite stimulants, antiemetics, antispasmodics, and have some analgesiceffects.[82] Five important cannabinoids found in the cannabis plant are tetrahydrocannabinol, cannabidiol, cannabinol, caryophyllene, and cannabigerol.
[edit] nly states to utilize dispensaries to sell medical cannabis. California's medical marijuana industry took in about $2 billion a year and generated $100 million in state sales taxes during 2008[189] with an estimated 2,100 dispensaries, co-operatives, wellness clinics and taxi delivery services in the sector colloquially known as cannabusiness.[190] On 19 October 2009 the US Deputy Attorney General issued a US Department of Justice memorandum to "All United States Attorneys" providing clarification and guidance to federal prosecutors in US States that have enacted laws authorizing the medical use of marijuana. The document is intended solely as "a guide to the exercise of investigative and prosecutorial

discretion and as guidance on resource allocation and federal priorities." The US Deputy Attorney General David W. Ogden provided seven criteria, the application of which acts as a guideline to prosecutors and federal agents to ascertain whether a patients use, or their caregivers provision, of medical marijuana "represents part of a recommended treatment regiment consistent with applicable state law", and recommends against prosecuting patients using medical cannabis products according to state laws. Not applying those criteria, the Dep. Attorney General Ogden concludes, would likely be "an inefficient use of limited federal resources". The memorandum does not change any laws. Sale of cannabis remains illegal under federal law. The U.S. Food and Drug Administration's position, that marijuana has no accepted value in the treatment of any disease in the United States, has also remained the same.[191] The Health and Human Services Division of the federal government holds a patent for medical marijuana. The patent, "Cannabinoids as antioxidants and neuroprotectants", issued October 2003[152] reads: "Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotectants, for example in limiting neurological damage following ischemic insults, such asstroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia..."[192] [edit]S

Introduction
It is generally accepted that chemical testing of biological fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biological specimen can be used to document exposure. The standard in drug testing is the immunoassay screen, followed by gas chromatographic-mass spec-trometric confirmation conducted on a urine sample. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological specimens, such as saliva, sweat, meconium and hair. The advantages of these samples over traditional media, like urine and blood, are obvious: collection is almost noninvasive, is relatively easy to perform, and in forensic situations may be achieved under close supervision of law enforcement officers to prevent adulteration or substitution. Moreover, the window of drug detection is dramatically extended to weeks, months or even years. The aim of this article is to document the usefulness of these alternatives in forensic situations. Hair testing for drugs of abuse in humans was first demonstrated in 1979 in the United States, and was rapidly followed by some German results. Since then, more then 300 papers have been published, most of them being devoted to analytical procedures. After

an initial period during which drugs were analyzed using immunological tests, the standard is now to use gas chromatography coupled with mass spectrometry. During the early stages of hair testing, opiates and cocaine were the predominant analytes, followed by amphetamine derivatives. Only recently have can-nabis, benzodiazepines and, very recently, doping agents been evaluated. Hair analysis was initially developed to document forensic cases; however, today, numerous applications have been described in clinical, occupational and sporting situations.

Incorporation of Drugs in Hair

This is one of the major points of disagreement among scientists actively involved with hair analysis. The time at which a drug appears in hair after administration is highly variable. According to several authors, this delay can be some hours or even days. Based on these differences, a complex model has been proposed to account for drug incorporation. Both sweat and sebum have been suggested to complement blood in this process but the exact mechanism is still under discussion. It has been demonstrated that, for the same administered dose, black hairincorporates more drug than blond hair, clearly indicating the influence of melanin. For some authors, these findings suggest a racial element in haircomposition. Cosmetic treatments, like bleaching or waving, affect the drug content, producing a 50-80% reduction in the original concentration. In almost all cases, the major compound detected in hair is the parent drug, much more so than its metabolites. For example, cocaine is present at concentrations 5-10 times greater than benzoylecgonine, and 10-30 times greater than ecgonine methylester, although, in blood, both metabolites are found at higher concentrations than cocaine. The very short halflife of heroin and 6-acetylmorphine makes their detection quite impossible in blood, but these two compounds are found in larger amounts than morphine in hair. This is also the case for sweat, and thus confirms the implication of sweat in the incorporation of drug in hair. Environmental contamination has also been proposed as a potential risk of incorporation, leading to false positives. Drugs that are smoked, like cannabis,crack or heroin, are of concern, and it is therefore necessary to include a decontamination step to eliminate false-positive findings. Various procedures have been described in the literature: these involve the use of organic solvents, aqueous solutions or a sequence ofsolvent and buffer. To minimize the influence of external contamination, several authors have proposed various appraches including an analysis of the wash solution, or to carry a kinetic of the wash ratios. Others have proposed the identification of specific or unique metabolites, such as norcocaine or cocaethylene, a compound that is formed when concomitant cocaine and ethanol are used. The detection of specific markers is not easy, as their concentrations in hair are generally low. Therefore, some authors have proposed the use of drug ratios, like morphine-codeine, to document heroin abuse, or benzoylecgoninecocaine greater than 0.05, to document cocaine abuse. Finally, positive cutoffs have

been published to insure international uniformity (Table 1). After collection, the hair specimen is best stored at ambient temperature. Once incorporated in hair, drugs are very stable. Cocaine and benzoylecgonine have been detected in hair from Peruvian mummies, clearly demonstrating 500 years of stability.

Hair Collection and Analysis

Strands of hair (about 60 to 80) are cut as close as possible to the skin, in the posterior vertex region, dried and stored in tubes at room temperature. The root-to-end direction must be indicated. In the case of very short hair, pubic hair can also be collected. Typical hair preparation involves the following steps: decontamination of the strand in organic solvent or buffer; pulverization of 100 mg in a ball-mill; hydrolysis of a 50 mg sample in acid or alkaline buffer; purification by solid-phase or liquid-liquid extraction; derivatization; analysis with gas chromatography coupled with mass spectrometry (GC-MS).

Table 1 Proposed positive cutoffs

Analytes Heroin Cocaine Amphetamine, MDMA Cannabis Cutoff (ng mg 1) 0.5 for 6-acetylmorphine 0.5 for cocaine 0.5 for both drugs Not decided

Care is necessary to prevent the conversion of cocaine to ecgonine, or 6-acetylmorphine to morphine, in alkaline solution. Differences in efficiency between enzymatic and acid hydrolysis are not statistically significant. A critical element in the acceptance of hair analysis for detection of drugs of abuse is laboratory performance. Laboratories must be able to demonstrate that they can accurately determine what drugs are present in unknown hair samples and at what concentrations. Several international interlaboratory comparisons of qualitative and quantitative determinations of drugs have been organized in the United States (National Institute of Standards and Technologies, Gaithersburg, MD) and Europe (Society of Hair Testing, Strasbourg, France). Interlaboratory comparisonsof hair analysis have been published for opiates, cocaine, cannabis and amphetamines. In most cases, GC-MS was used for the analyses. However, no one extraction method could be identified as being superior to others. In 1999, the following compounds were reported to be detectable in hair:drugs of abuse (opiates, cocaine, cannabis, amphetamines, methadone, phencyclidine, narcotics); pharmaceuticals (barbiturates, antidepressants, benzodiazepines, neuroleptics, etc.); nicotine; doping agents (p-adrenergic drugs, anabolic steroids and

corticosteroids); pesticides. Measured concentrations are expressed in picograms or nanograms per microgram.

Detection of Drugs of Abuse in Hair Opiates

Three methods of screening for opiates, cocaine, cannabinoids and amphetamine, including its derivatives, dominate in the literature; these are briefly described in Table 2. Liquid-liquid extraction after HCl hydrolysis and solidphase extraction after enzymatic hydrolysis with p-glucuronidase/sulfatase lead to similar results, both with the disadvantage that heroin and 6-O-acetylmorphine (MAM) might be hydrolyzed to morphine. The methanol method is undoubtedly the simplest, with high sensitivity for heroin and cocaine but poor sensitivity for their metabolites, morphine and benzoylecgonine; and high sensitivity for A9-tetrahydrocannabinol (THC) but no sensitivity for THC-COOH. In 1995, it was confirmed by systematic extraction studies that methanol and water had the best extraction capability for opiates, but using hydrophobic solvents like dioxane and acetonitrile, a low extraction rate was found. With toluene, almost no extraction occurred. The range of positive results using these procedures is listed in Table 3. Pubic hair showed higher drug levels than scalp hair. This can be due to the slightly lower growth rate of pubic hair than scalp hairbut, additionally, pubic and scalp hair have totally different telogen:anagen ratios and concentrations cannot be directly compared. Regarding individual growth rate and the problem of telogen:anagen ratios, dose-concentration relation studies should only be performed with hair samples grown from the shaved skin before drug administration and under control of the growth speed of the hair.

Table 2 Screening procedures for the detection of illegal drugs in hair

Kauert (1996) Analytes Kintz (1995) Heroin, 6-MAM, Heroin, 6-MAM, Moeller (1993) Heroin, 6-MAM, dihydrocodeine, codeine, methadone, THC, cocaine, amphetamine, MDMA, MDEA, MDA 20 ml H20(2x) 20ml acetone

dihydrocodeine, dihydrocodeine, codeine, codeine, methadone, THC, methadone, THC, cocaine, cocaine, amphetamine, amphetamine, MDMA, MDMA, MDEA, MDA MDEA, MDA Decontamination Ultrasonic 5 min 5 ml Cl2CH2 step each 5 ml H20 (2 x 5 min) 5 ml acetone 5 ml petrolether 100 mg hair cut Homogenization into small sections Ball-mill in a 30 ml vial Extraction 4 ml methanol 50mg powdered hair, 1 ml 0.1

Ball-mill 20-30 mg

ultrasonic 5 h at 50C N HCl, 16hat56C (NH4)2HP04; extraction 10 ml CHCl3/2-propanol/n-hepta-ne (50:17:33); organic phase purified with 0.2 N HCl; HCl phase to pH 8.4; reextraction with CHCl3 40 nl BSTFA/1% TMCS; 20min at 70 C

powdered hair, 2 ml acetate buffer + pglucuronidase/ arylsulfatase, 90min at 40C NaHC03; SPE (C18), elution with 2 ml acetone/CH2Cl2 (3:1) 1000 nl PFPA/75 nl PF-n-propanol; 30min at 60C; N2 at 60C; 50 nl ethylacetate

Clean-up

None

Derivatization

Propionic acid anhydride

In hair specimens of 20 subjects receiving intravenous heroin hydrochloride, no correlation between the doses administered and the concentrations of total opiates in hair was observed. However, when considering a single analyte, it was noted that the correlation coefficient seemed to be linked to its plasma half-life. A weak correlation coefficient corresponds to a drug with a short plasma half-life, and the correlation coefficient increases when plasma half-life increases, from heroin, 6-acetylmorphine to morphine. The so-called poppy seed problem could by solved by examining hair for morphine after poppy seed ingestion, as morphine is not detected in hairafter consumption of seeds, or at least only in traces.

Cocaine
The fact that the parent drug is found in higher concentrations in the hair of drug users has been well known since 1991. Typical concentration ranges are listed in Table 4. Contrary to the case in heroin abuse, cocaine consumption can be detected by measurable metabolites which cannot be caused by cocaine contamination, like norcocaine or cocaethylene. The determination of the pyrolysis product of cocaine, the anhydroecgonine methyl ester (AEME), can be helpful in distinguishing cocaine and crack users. The literature and the scientific meetings concerning cocaine are dominated by discussion as to whether decontamination procedures can remove external contamination completely, and whether a racial element exists. This is important when hair analysis is used as stand-alone evidence for workplace testing.

Table 3 Published ranges of 6-O-acetylmorphine concentration in the hair of heroin users

Authors Concentration (ngmg 1) Kauert (1996) 0.03-79.8 Kintz (1995) 0-84.3

Moeller (1993) 2.0-74 Pepin (1997) 0.3-131.2

Table 4 Published ranges of cocaine concentration in the hair of drug users

Authors Kauert (1996) Kintz (1995) Moeller (1993) Pepin (1997) Concentration (ng mg 1) 0.04-129.7 0.4-78.4 0.3-127.0 0.89-242.0

An important study with controlled doses of cocaine-ii5 was published in 1996. The deuterium-labeled cocaine was administered intravenously and/ or intranasally in doses of 0.6-4.2 mg kg-1 under controlled conditions. A single dose could be detected for 2-6 months; the minimum detectable dose appeared to be between 22 and 35 mg; but within the range of doses used in the study, the hair test did not provide an accurate record of the amount, time or duration of drug use. Cocaine, benzoylecgonine and ecgonine methyl-ester have also been found in the mummified bodies of ancient Peruvian coca-leaf chewers. In contrast to todays cocaine users, the cocaine:benzoylecgonine ratio was less than 1.

Cannabis
In 1996, the first results on levels of cannabis in hair measured by using GC-MS were reported, simultaneously with the determination in the same run of THC and its major metabolite THC-COOH. The measured concentrations were low, particularly in comparison with other drugs. Some authors suggested the use of negative chemical ionization to target the drugs, or the application of tandem mass spectrometry. More recently, a simpler method was proposed, based on the simultaneous identification of cannabinol, cannabidiol and THC. This procedure appears to be a screening method that is rapid and economical and does not require derivatization prior to analysis. As THC, cannabinol and cannabidiol are present in smoke, to avoid potential external contamination the endogenous metabolite THC-COOH should be secondarily tested to confirm drug use. As shown in Table 5, the concentrations measured are very low, particularly for THCCOOH, which is seldom identified. To date, there is no consensus on cutoff values for cannabis. An international debate must be held to discuss the differences noted between

Table 5 Reported concentrations for cannabis in hair

Authors Compound Number of positives Concentration (ng/mg) Cairns (1995) THC-C00H + 3000 (0.0007) Jurado (1995) THC 298 0.06-7.63 (0.97) THC-C00H 298 0.06-3.87 (0.50) Kauert (1996) THC 104 0.009-16.70 (1.501) Kintz (1995) THC 89 0.10-3.39(0.64) Cannabidiol 306 0.03-3.00 (0.51)

Cannabinol THC-C00H Moeller (1993) THC THC-C00H Wilkins (1995) THC

268 267 10 2 8

0.01-1.07(0.16) 0.05-0.39(0.10) 0.4-6.2 (2.0) 1.7-5.0(3.3) 0.03-1.1

American laboratories, which reported THC-COOH in the low picogram per milligram range, and some European laboratories, which gave concentrations in the low nanogram per milligram range, as is obvious from the measured concentrations shown.

Amphetamine derivatives
Almost all of the literature dealing with amphetamines in hair has been written by Japanese researchers. In most cases, amphetamine and methamphtetamine have been the target drugs. More recently, particular attention has been focused on methylenedioxy-amphetamine (MDA) derivatives, like methylenedi-oxymethamphetamine (MDMA). Most techniques published used acid or alkaline hydrolysis, or a combination of hydrochloric acid and methanol, followed by a purification step (liquidliquid extraction or solid-phase extraction) and derivatization. When comparing four different procedures for amphetamine, MDA and MDMA (methanol sonica-tion, acid hydrolysis, alkaline hydrolysis and enzymatic hydrolysis) it was demonstrated that best recovery rates were observed after alkaline hydrolysis; however, it was not possible to determine which method performed best, based on recovery rate, precision and practicability. Lower concentrations were observed after methanol sonication, together with dirty chromatograms. It must be pointed out that, since the first identification of MDMA in human hair in 1992, this compound, particularly in Europe, is one of the most frequently identified and must therefore be included in all screening procedures. Typical findings for amphetamine derivatives are given in Table 6. Although there are still controversies surrounding the interpretation of results, particularly concerning external contamination, cosmetic treatments, ethnic bias or drug incorporation, pure analytical work in hair analysis has more or less reached a plateau, having solved almost all the analytical problems. Conferences on hair analysis in Genoa, Strasbourg, Tampa and Abu Dhabi, between 1992 and 1996, indicate the increasing role of this method for the investigation of drug abuse.

Table 6 Analytical parameters and results for a general screening procedure for amphetamine derivatives
Compound Ions monitored (m/z) Linearity (r) 0.998 0.995 0.994 0.996 0.997 Amphetamine 91, 118, 240 Methamphetamine 169, 210, 254 MDA 135, 240, 375 MDMA 210, 254, 389 MDEA 240, 268, 403 Precision Concentration (at2ngmg-1,%) (ngmg-1) 6.9 2.3-20.6 (n = 5) 8.4 9.1 0.4-8.0 (n = 13) 10.2 0.3-42.7 (n = 14) 13.0 0.6-69.3 (n = 6)

MBDB BDB

176, 268, 403 135, 176, 389

0.994 0.996

8.7 9.4

1.41-3.09 (n = 2) 0.21 (n =1)

Applications
In the case of segmental analysis, to evaluate the pattern of drug abuse for example, proximal and distal portions of hair must be identified. Given the variation in hair growth rates, generally 1.0-1.3 cm per month, results from a multisectional analysis should not be used to determine a precise period of drug exposure. The further away from the hair root, the more cautious the interpretation of quantitative findings of the individualhair sections must be. Table 7 lists the major characteristics of both urine and hair analyses.The major practical advantage of hair testing compared with urine testing for drugs is its larger surveillance window: weeks to months in hair, depending on the length of the hair shaft, versus 2-4 days in urine for most xenobiotics, except can-nabis. In fact, for practical purposes, the two tests complement each other. Urinalysis provides short-term information on an individuals drug use, whereas long-term histories are accessible through hair analysis. While analysis of urine specimens cannot distinguish between chronic use or single exposure, hair analysis makes this distinction. Its greatest use, however, may be in identifying false negatives, as neither abstaining from a drug for a few days nor trying to beat the test by diluting urine will alter the concentration in hair. Urine does not indicate the frequency of drug intake in subjects, who might deliberately abstain for several days before screening. It is always possible to obtain a fresh, identical hair sample if there is any claim of a specimen mix-up or breach in the chain of custody. This makes hair analysis essentially failsafe, in contrast to urinalysis, as an identical urine specimen cannot be obtained at a later date. Clearly, hairanalysis can thus function as a safety net for urinalysis. Numerous forensic applications have been described in the literature where hair analysis was used to document the case:differentiation between a drug dealer and a drug consumer, chronic poisoning, crime under the influence of a drug, child sedation, child abuse, doubtful death, child custody, abuse ofdrugs in jail, body identification, survey of drug addicts, chemical submission, obtaining a driving license and doping control. It appears that the value of hair analysis for the identification of drug users is steadily gaining recognition. This can be seen from its growing use in preemployment screening, in forensic sciences and in clinical applications. Hair analysis may be a useful adjunct to conventional drug testing in toxicology. Methods for evading urinalysis do not affect hair analysis. Specimens can be more easily obtained with less embarrassment, andhair can provide a more accurate history of drug use. Costs are too high for routine use but the generated data are extremely helpful in documenting positive cases.

Table 7 Comparison between urine and hair for testing drugs of abuse
Parameter Drugs Urine All Hair All

Major compound Metabolites Parent drug Detection period 2-4 days, except cannabis Weeks, months Type of measure Incremental Cumulative Screening Yes Yes Invasiveness High Low Storage -20 C Ambient temperature Risk of false negative High Low Risk of false positive Low Undetermined Risk of adulteration High Low Control material Yes Yes Determination of Cannabinoids in Hair
Sat, 24 Sep 2011 20:38:58 | Natural Cannabis Determination of drugs in hair has continued to grow in importance; its advantages over analysis of other matrices are that it is relatively noninvasive, and drugs can be detected in hair for a much longer time period. However, cannabinoids in blood are not taken up in hair nearly as efficiently as most other drugs are. As a result, concentrations of cannabinoids in hair after smoking or ingestion of marijuana are very low and can only be detected with extremely sensitive analytical methods. Furthermore, cannabinoid metabolites such as THCA are normally present in hair at even lower concentrations than parent cannabinoids such as THC, cannabinol, and canna-bidiol. This is a problem in forensic cases because passive exposure to marijuana smoke can result in external adsorption of cannabinoids to hair follicles. Consequently, a hair analysis that detects THCA provides more convincing evidence of intentional smoking or ingestion of marijuana than a hair analysis that detects THC, cannabinol, or cannabidiol. However, a strong case can be made for intentional marijuana use based on detection of THC, cannabinol, or cannabidiol if it is shown that the method of decontamination removes all externally adsorbed cannabinoids from the hair prior to hair analysis. Most published reviews on testing for drugs in hair primarily discuss methods for analysis of basic drugs such as cocaine, opiates, and amphetamines. Authors who have reviewed analysis of cannabinoids in hair include Staub (6), Sachs and Kintz (59), and Baptista et al. (60). Methods for the determination of cannabinoids in hair generally include the following basic steps: (1) decontamination of hair by washing with a solvent to remove any cannabinoids adsorbed to external surfaces of the hair; (2) enzymatic or alkaline hydrolysis of the hair to facilitate extraction of the cannabinoids; (3) extraction of the digested hair; (4) derivatization of the extracted cannabinoids; and (5) analysis using GC and MS. The cannabinoids that appear to have the highest concentration in hair are THC, cannabinol, and cannabidiol. However, some of the published methods are designed to detect only THCA, for reasons stated above.

Methylene chloride has been most often used for decontaminating hair prior to digestion (6164); however, Strano-Rossi and Chiarotti reported that washing with petroleum ether was more efficient than methylene chloride for then removal of cannabinoids adsorbed to hair (65). Wilkins et al. compared four different wash solvents (methylene chloride, methanol, isopropanol, and phosphate buffer) for analysis of THC in human hair from known cannabis users. The concentrations of THC were significantly lower when methylene chloride was used (66). To extract cannabinoids efficiently, the hair is first dissolved by alkaline hydrolysis or by enzymatic hydrolysis. Alkaline hydrolysis is generally favored because it can be performed very rapidly. After addition of internal standard(s) the hair is subjected to NaOH (1-2 N) at 80-95C for 10-30 minutes (61-65,67) or maintained at 37C overnight (66). If the assay includes determination of drugs that are degraded in the presence of strong alkali, P-glucuronidase/arylsulfatase can be used to digest the hair prior to extraction (60). Early methods for the determination of cannabinoids in hair used liquid/liquid extraction to remove cannabinoids from the hydrolyzed hair (61-63,66,68); for example, after acidification, homogenized hair can be extracted with hexane:ethyl acetate (9:1 v/v; ref. 61). A more recently published method employing enzymatic hydrolysis used a two-step liquid/liquid extraction procedure (60). After adjustment of the pH to 8.5, the hydrolyzed hair sample was extracted with chloroform:isopropanol (97:3 v/v). The aqueous layer was separated, acidified with acetic acid, and re-extracted with hexane:ethyl acetate (9:1 v/v). The two organic extracts were then combined and prepared for GC/MS analysis. Sachs and Dressler developed a very sensitive but lengthy assay for the detection of THCA in hair. The procedure involved initially extracting the hydrolyzed hair in hexane:ethyl acetate, washing the organic extract with 0.5 M NaOH and then with 0.1 M HCl, and injecting the concentrated organic extract into a high-performance liquid chro-matography column. The fraction containing THCA was collected, acidified with 0.05 M phosphoric acid, and extracted with hexane:ethyl acetate. This extensive clean-up permitted detection of derivatized THCA at concentrations as low as 0.3 pg/mL (67). Other recently published methods have generally used SPE procedures, including solid-phase microextraction (SPME). Moore et al. used mixed-mode hydrophobic/anion exchange SPE cartridges to extract THCA from digested hair (64). After conditioning the SPE cartridge, the hydrolyzed hair sample was added to the cartridge; the column was washed with deionized water (2 mL) and 0.1 M HCl:acetonitrile (70:30 v/v; 2 mL) and dried, after which THCA was eluted with 3 mL of hexane:ethyl acetate (75:25 v/v). Several variations of solid-phase microextractions have recently been used to extract cannabinoids from hydrolyzed hair samples. Strano-Rossi and Chiarotti developed a relatively

simple and rapid method for detection of THC, cannabinol, and can-nabidiol in hair based on solid-phase microextraction and GC/MS analysis (65). A commercially available 30-|m polydimethylsiloxane fiber was dipped into the neutralized hair digest for 15 minutes and then inserted directly into the injection port of the GC/MS, where the adsorbed nonderivatized cannabinoids were vaporized. The injection port temperature was 260C; the 5% phenylmethylsilicone capillary column was maintained at 100C for 2 minutes and then temperature-programmed to 270C. The LODs for analysis of 50 mg of hair were 0.1 ng/mg for THC and cannabinol and 0.2 ng/mg for cannabidiol. Musshoff et al. used two variations of a headspace solid-phase microextraction (HS-SPME) method for determination of cannabinoids in hair. With one method a 100-|m polydimethylsiloxane fiber was inserted for 25 minutes into the headspace of a heated (90C) vial containing the digested hair (69). The fiber was then exposed to the headspace in a second vial containing 25 |L of MSTFA for 8 minutes at 90C, resulting in trimethylsilylation of the adsorbed cannabinoids. Finally, the fiber was inserted into the heated (250C) injection port of a GC/MS, permitting the derivatized cannabinoids to be vaporized and analyzed. The reported LODs ranged from 0.05 to 0.14 ng/mg for THC, cannabidiol, and cannabinol. THCA w

Was not detected. Drug Classification:

Introduction to Drug Ac

Definition: Drugs can be classified according to various criteria including chemical structure or pharmacological action. The preferred A very broad definition of a drug wou classification is the latter one which may be divided into main groups include "all chemicals other than food as follows: affect living processes." If the affect h the body, the drug is a medicine. How a) Chemotherapeutic agents - used to cure infectious diseases and a drug causes a harmful effect on the b cancer. (Sulfa drugs, Antibiotics) the drug is a poison. The same chemic b) Pharmacodynamic agents - used in non-infectious diseases be a medicine and a poison depending (Cholinergic, Adrenergic, Hallucinogenic, Sedatives) conditions of use and the person using c) Miscellaneous agents (Narcotic Analgesics, Local Anesthetics) Another definition would be "medicin Drug Names: agents used for diagnosis, prevention, treatment of symptoms, and cure of Drugs have three or more names including a: chemical name, brand or diseases." Contraceptives would be ou trade name, and generic or common name. The chemical name is of this definition unless pregnancy we assigned according to rules of nomenclature of chemical compounds. considered a disease. The brand name is always capitalized and is selected by the manufacturer. The generic name refers to a common established name Disease Classification: irrespective of its manufacturer. A disease is a condition of impaired h In most cases, a drug bearing a generic name is equivalent to the same resulting from a disturbance in the stru drug with a brand name. However, this equivalency is not always true. or function of the body. Diseases may

classified into the following major categories:

Although drugs are chemically equivalent, different manufacturing processes may cause differences in pharmacological action. Several differences may be crystal size or form, isomers, crystal hydration, purity-(type and number of impurities), vehicles, binders, coatings, dissolution rate, and storage stability.

1) Infections caused by viruses, ricke bacteria, fungi, protozoa and worms 2) Allergic diseases caused by antigen foreign substances 3) Metabolic disorders caused by def the body's ability to carry out normal reactions - these may be hereditary, deficiency, and congenital defects 4) Cancer 5) Toxic diseases caused by poisons 6) Psychosomatic and mental diseas

Chemotherapy, broadly defined, mean treatment of any disease by chemicals including infectious and non-infectiou diseases. The original definition appli to drugs which were used in the treatm infectious diseases. The proper term fo treatment of non-infectious diseases is pharmacodynamics.

Sites of Drug Action: l. Enzyme Inhibition: Drugs act within the cell by modifying normal biochemical reactions. Enzyme inhibition may be reversible or non reversible; competitive or non-competitive. Antimetabolites may be used which mimic natural metabolites. Gene functions may be suppressed. 2. Drug-Receptor Interaction: Drugs act on the cell membrane by physical and/or chemical interactions. This is usually through specific drug receptor sites known to be located on the membrane. A receptor is the specific chemical constituents of the cell with which a drug interacts to produce its pharmacological effects. Some receptor sites have been identified with specific parts of proteins and nucleic acids. In most cases, the chemical nature of the receptor site remains obscure. 3. Non-specific Interactions: Drugs act exclusively by physical means outside of cells. These sites include external surfaces of skin and gastrointestinal tract. Drugs also act outside of cell membranes by chemical interactions. Neutralization ofstomach acid by antacids is a good example.

Introduction to Drug Action

Definition: A very broad definition of a drug would include "all chemicals other than food that affect living processes." If the affect helps the body, the drug is a medicine. However, if a drug causes a harmful effect on the body, the drug is a poison. The same chemical can be a medicine and a poison depending on conditions of use and the person using it. Another definition would be "medicinal agents used for diagnosis, prevention, treatment of symptoms, and cure of diseases." Contraceptives would be outside of this definition unless pregnancy were considered a disease. Disease Classification: A disease is a condition of impaired health resulting from a disturbance in the structure or function of the body. Diseases may be classified into the following major categories:

1) Infections caused by viruses, ricketsia, bacteria, fungi, protozoa and worms 2) Allergic diseases caused by antigens and foreign substances 3) Metabolic disorders caused by defects in the body's ability to carry out normal reactions - these may be hereditary, deficiency, and congenital defects 4) Cancer 5) Toxic diseases caused by poisons 6) Psychosomatic and mental diseases Chemotherapy, broadly defined, means the treatment of any disease by chemicals including infectious and non-infectious diseases. The original definition applied only to drugs which were used in the treatment of infectious diseases. The proper term for the treatment of non-infectious diseases is pharmacodynamics. Introduction to Drugs of Abuse: Cocaine, Opiates (Heroin) and Marijuana (THC) For Teachers and Learners (Annotations include tips on "How One Would Teach This Lesson") Right click>open Link in New Tab>for Full View

1: Introduction First I will explain how the brain basically works and how drugs such as cocaine, opiates and marijuana interact with the brain's normal activities. I will introduce the concept of "reward" which is the property that is characteristic of many addictive drugs. Note the brain is a functional unit; it is made up of billions of nerve cells

(neurons) that communicate with each other using electrical and chemical signals.

2: Brain regions and neuronal pathways Certain parts of the brain govern specific functions. Point to sensory, motor, association and visual cortex to highlight specific functions. Point to the hippocampus to highlight the region that is critical for memory, for example. Indicate that nerve cells or neurons travel from one area to another via pathways to send and integrate information. Show, for example, the reward pathway. Start at the ventral tegmental area (VTA) (in blue), follow the neuronal path to the nucleus accumbens (purple), and then on to the frontal cortex. Explain that this pathway gets activated when a person receives positive reinforcement for certain behaviors ("reward"). Indicate that you will explain how this happens when a person takes an addictive drug.

3: Neuronal structure Remind the student that pathways are made up of neurons. Describe the anatomy of a neuron (soma, dendrites, and axon are marked with text). State that this neuron is real - as viewed through a microscope. Explain the normal direction of impulse flow. Dendrites and soma receive chemical information from neighboring neuronal axons. The chemical information is converted to electrical currents which travel toward and converge on the soma. A major impulse is produced (the action potential) and travels down the axon toward the terminal. Point to the terminal.

4: The synapse and synaptic neurotransmission Describe the synapse and the process of chemical

neurotransmission. Indicate how vesicles containing a neurotransmitter, such as dopamine (the stars), move toward the presynaptic membrane as an electrical impulse arrives at the terminal. Describe the process of dopamine release (show how the vesicles fuse with the presynaptic membrane). Once inside the synaptic cleft, the dopamine can bind to specific proteins called dopamine receptors (in blue) on the membrane of a neighboring neuron. Introduce the idea that occupation of receptors by neurotransmitters causes various actions in the cell; activation or inhibition of enzymes, entry or exit of certain ions. State that you will describe how this happens in a few moments.

5: Dopamine and the production of cyclic AMP Using the close-up view, explain what happens when dopamine binds to its receptor. When dopamine binds to its receptor, another protein called a G-protein (in pink) moves up close to the dopamine receptor. The G-protein signals an enzyme to produce cyclic adenosine monophosphate (cAMP) molecules (in green) inside the cell. [Sometimes the signal can decrease production of cAMP, depending on the kind of dopamine receptor and G-protein present.] Point to the dopamine receptor-G-protein/adenylate cyclase complex, and show how cAMP is generated when dopamine binds to its receptor. Indicate that cAMP (point to the cyclic-looking structures) controls many important functions in the cell including the ability of the cell to generate electrical impulses.

6: Summary of neuronal transmission Use the example of two neurons making contact to summarize neuronal transmission. Point to the cell on the top and indicate that electrical impulses flow in the direction toward the terminal. Remind the students what happens when impulses reach the terminal; neurotransmitters are released, they bind to their receptors, and new impulses are generated in the cell on the bottom. Explain that this is how information travels from neuron to neuron.

7: Reward: drug self-administration Introduce the concept of positive reinforcement or reward. Explain that rats will press a lever to self-administer an injection of cocaine or heroin that is inserted into either the peripheral

bloodstream (left image) or into specific brain regions (right image). The rat keeps pressing to get more cocaine or heroin because the drugs make the rat feel so good. This is called positive reinforcement, or reward. Natural rewards include food, water, and sex - each is required to maintain survival of our species. Animals and people will continue to exhibit a behavior that is rewarding, and they will cease that behavior when the reward is no longer present. Explain that there is actually a part of the brain that is activated by natural rewards and by artificial rewards such as addictive drugs. This part of the brain is called the reward system. Neuroscientists have been able to pinpoint the exact parts of the brain involved, with the help of the rats. Point to the cartoon on the right and explain that rats will also selfadminister addictive drugs directly into their brains, but only into a specific area of the reward system. If the injection needle is moved less than a millimeter away from this crucial area, the rat won't press the lever for more drug. So based on information from working with the rats, scientists have drawn a map of the brain, and located the structures and pathways that are activated when an addictive drug is taken voluntarily. Tell the students that you will show them this "map."

8: The reward pathway Tell students that this is a view of the brain cut down the middle. An important part of the reward system is shown and the major structures are highlighted: the ventral tegmental area (VTA), the nucleus accumbens (nuc. acc.) and the prefrontal cortex. Also,

the pathway connecting these structures is highlighted. The information travels from the VTA to the nucleus accumbens and then up to the prefrontal cortex. Reiterate that this pathway is activated by a rewarding stimulus. [Note to scientists - this is not the only pathway activated by reward, other structures are involved too, but only this part of the pathway is shown for simplicity.]

9: Injection of cocaine into the nucleus accumbens Demonstrate how scientists located the structures important for the addictive nature of drugs. Show that a rat will self-administer cocaine directly into the nucleus accumbens (or the VTA) to activate the pathway. Point to an area close to the nucleus accumbens or VTA and state that if the injection is placed in this other area, the rat will not press the lever to receive the drug. Indicate that scientists know a lot more than where the drug acts to produce rewarding effects - they also know how the drugs work. Show examples with cocaine, heroin, and marijuana.

10: Localization of cocaine "binding sites" When a person smokes or snorts cocaine, it travels quickly to the brain. Although it reaches all areas of the brain, it concentrates in some specific areas. These are highlighted with the turquoise sprinkles; the VTA, the nucleus accumbens, and the caudate nucleus (lighter turquoise since the caudate is inside the hemisphere). Point out that cocaine concentrates especially in the reward areas that you have just discussed. Cocaine accumulation in other areas such as the caudate nucleus can explain other effects such as increased stereotypic behaviors (pacing, nailbiting, scratching, etc..)

14: Positron emission tomography (PET) scan of a person on cocaine

Cocaine has other actions in the brain in addition to activating reward. Scientists have the ability to see how cocaine actually affects brain function in people. The PET scan allows one to see how the brain uses glucose; glucose provides energy to each neuron so it can perform work. The scans show where the cocaine interferes with the brain's use of glucose - or its metabolic activity. The left scan is taken from a normal, awake person. The red color shows the highest level of glucose utilization (yellow represents less utilization and blue shows the least). The right scan is taken from a cocaine abuser on cocaine. It shows that the brain cannot use glucose nearly as effectively - show the loss of red compared to the left scan. There are many areas of the brain that have reduced metabolic activity. The continued reduction in the neurons' ability to use glucose (energy) results in disruption of many brain functions.

15: Localization of opiate binding sites When a person injects heroin or morphine, it too travels quickly to the brain. Point to the areas where opiates concentrate. The VTA, nucleus accumbens, caudate nucleus and thalamus are highlighted. The opiates bind to opiate receptors that are concentrated in areas within the reward system. Indicate that the action of opiates in the thalamus contributes to their ability to produce analgesia.

16: Opiates binding to opiate receptors in the nucleus accumbens: increased dopamine release Show how opiates activiate the reward system using the nucleus accumbens as an example. Explain that the action is a little more complicated than cocaine's because more than two neurons are involved. Point out that three neurons participate in opiate action: the dopamine terminal, another terminal (on the right) containing a different neurotransmitter (probably GABA for those that would like to know), and the post-synaptic cell containing dopamine receptors. Show that opiates bind to opiate receptors (green) on the neighboring terminal and this sends a signal to the dopamine terminal to release more dopamine. [In case an inquisitive student asks how, one theory is that opiate receptor activation decreases GABA release, which normally inhibits dopamine release, so dopamine release is increased.]

17: Increased cAMP produced in post-synaptic cell In a closer view, again, show how this affects the function of the post-synaptic cell. Since there is more dopamine released, there is increased activation of dopamine receptors, similar to the effect of cocaine. This causes increased production of cAMP inside the post-synaptic cell, which alters the normal activity of the neuron.

18: Summary: opiate binding in nucleus accumbens and activation of the reward pathway Show the "big picture." As a result of opiate actions in the nucleus accumbens (point to the sprinkles of opiates in the nuc. acc.), there are increased impulses leaving the nucleus accumbens to activate the reward system (point to the frontal cortex). As with

cocaine, continued use of opiates makes the body rely on the presence of the drug to maintain rewarding feelings and other normal behaviors. The person is no longer able to feel the benefits of natural rewards (food, water, sex) and can't function normally without the drug present.

19: Localization of THC binding sites When a person smokes marijuana, the active ingredient, cannabinoids or THC, travels quickly to the brain. Point to the areas where THC (magenta) concentrates. The VTA, nucleus accumbens, caudate nucleus, hippocampus, and cerebellum are highlighted. THC binds to THC receptors that are concentrated in areas within the reward system as well as these other areas. Indicate that the action of THC in the hippocampus explains its ability to interfere with memory and actions in the cerebellum are responsible for its ability to cause incoordination and loss of balance.

20: THC binding to THC receptors in the nucleus accumbens: increased dopamine release [Note to scientists - the interaction of THC with the reward system is not fully understood at this point. The following discussion is based on recent data, but additional theories may emerge as we obtain more data.] State that scientists know the least about THC. Over the last few years, there has been intense study to discover where and how THC works. One theory is that it acts in a similar way to opiates. Again use the nucleus accumbens as an example. The same three neurons are probably involved: the dopamine terminal, another terminal (on the right) containing a different neurotransmitter (probably GABA), and the post-synaptic cell containing dopamine receptors. Ask the students if they can tell you how THC might work. THC binds to THC receptors (magenta) on the neighboring terminal and this sends a signal to the dopamine terminal to release more dopamine. [Again, it is probably a presynaptic receptor on GABA interneurons that controls dopamine release.]

21: Increased cAMP produced in post-synaptic cell In a closer view, show how this affects the function of the postsyanaptic cell. Since there is more dopamine released, there is increased activation of dopamine receptors. This causes increased production of cAMP inside the post-synaptic cell which alters the normal activity of the neuron.

22: Summary: THC binding in nucleus accumbens and activation of the reward pathway Show the "big picture." As a result of THC actions in the nucleus accumbens (point to the concentration of THC in the nuc. acc.), there are increased impulses leaving the nucleus accumbens to activate the reward system (point to the frontal cortex). Scientists

still don't know how the continued use of marijuana alters the reward system. Indicate that this is an area of intense research by neuroscientists.

23: Overall summary: these drugs of abuse all activate the reward system via increasing dopamine neurotransmission In this last image, the binding of all three drugs is shown in one of the reward areas, the nucleus accumbens. Summarize that each drug increases the activity of the reward pathway by increasing dopamine transmission. This happens even though the drugs act by different mechanisms. Because of the way our brains are designed, and because these drugs activate a particular brain pathway for reward, they have the ability to be abused. Start a discussion; ask the students if they can think of any other drugs that are abused that probably activate the reward system in the same way. Answer: alcohol, nicotine, and amphetamine are good examples. Reference Resource: http://ncadistore.samhsa.gov/catalogNIDA/
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Sites of Drug Action: l. Enzyme Inhibition: Drugs act within the cell by modifying normal biochemical reactions. Enzyme inhibition may be reversible or non reversible; competitive or non-competitive. Antimetabolites may be used which mimic natural metabolites. Gene functions may be suppressed. 2. Drug-Receptor Interaction: Drugs act on the cell membrane by physical and/or chemical interactions. This is usually through specific drug receptor sites known to be located on the membrane. A receptor is the specific chemical constituents of the cell with which a drug interacts to produce its pharmacological effects. Some receptor sites have been identified with specific parts of proteins and nucleic acids. In most cases, the chemical nature of the receptor site remains obscure. 3. Non-specific Interactions: Drugs act exclusively by physical means outside of cells. These sites include external surfaces of skin and gastrointestinal tract. Drugs also act outside of cell membranes by chemical interactions. Neutralization ofstomach acid by antacids is a good example. Mode of Drug Action:

It is important to distinguish betwee actions of drugs and their effects. A of drugs are the biochemical physio mechanisms by which the chemical produces a response in living organi The effect is the observable consequ of a drug action. For example, the ac penicillin is to interfere with cell wa synthesis in bacteria and the effect i death of the bacteria.

One major problem of pharmacolog that no drug produces a single effec primary effect is the desired therape effect. Secondary effects are all othe effects beside the desired effect whi be either beneficial or harmful. Dru chosen to exploit differences betw normal metabolic processes and a abnormalities which may be present. Since the differences may very great, drugs may be nonspecifi action and alter normal functions as the undesirable ones. This leads to undesirable side effects.

The biological effects observed afte has been administered are the result interaction between that chemical an some part of the organism. Mechani drug action can be viewed from diff perspectives, namely, the site of acti the general nature of the drug-cell interaction. l. Killing Foreign Organisms:

Chemotherapeutic agents act by kill

weakening foreign organisms such a bacteria, worms, viruses. The main principle of action is selective toxici the drug must be more toxic to the p than to the host. 2. Stimulation and Depression:

Drugs act by stimulating or depressi normal physiological functions. Stimulation increases the rate of act while depression reduces the rate of activity.