ARIPIPRAZOLE
Aripiprazole was first approved in 2009 by Health Canada for the treatment of schizophrenia. Its current indications include the treatment of schizophrenia, major depressive order, and bipolar I disorder (manic depression). Harmful side effects that have arose from aripiprazole include compulsive or uncontrollable urges to gamble, binge eat, shop and have sex. These urges seem to leave after medication use is stopped. Aripiprazole acts as a dopamine partial agonist and serotonin antagonist to exert its effects. The mean elimination half life is around 75 hours and is eliminated mainly through hepatic metabolism.
AMPHETAMINE
Amphetamine was first used as an medical inhaler in 1933. It became a schedule II controlled substance in 1971 and is used in Canada as restrictive drug (schedule I) for medical treatment. Amphetamine is still illegally synthesized today in clandestine labs and sold on the black market to enhance physical performances and as a stimulant. Its side effects include addiction, hypertension, erectile dysfunction, and mood swings. Amphetamine belongs to the phenethylamine class. It is also the parent compound of its own structural class, the substituted amphetamines, which includes prominent substances such as bupropion, cathinone, MDMA, and methamphetamine.
BENZOYLEGNONINE
Benzoylecgonine is the primary metabolite of cocaine. It is formed by the liver by hydrolysis of cocaine and is then excreted in urine. It is therefore a good analyte for cocaine drug urine screening. Benzoylecgonine is not pharmacologically active.
BENZODIAZEPINES
Benzodiazepines were approved from the 1960s-70s and were developed as a safer alternative to barbiturates. They were often used as a sedative for their hypnotic, anxiolytic, anticonvulsant and muscle relaxant properties. Fatal overdoses can occur when benzodiazepines are taken with other central nervous system depressants. In addition, long-term use can lead to heavy dependence on the drug and withdrawal symptoms. Benzodiazepines work by increasing the effect of the inhibitory neurotransmitter GABA at the GABA receptor which in turn reduces brain activity. Benzodiazepines have different half lives depending on the specific compound and can be detected in urine from 2-7 days.
BIOTIN
The FDA currently does not have a daily recommended dietary allowance for biotin. Our body does need biotin to act as a coenzyme to metabolize carbohydrates, fats and amino acids. However, biotin is normally obtained from a healthy diet with biotin deficiency being extremely rare. It is also often advertised as a hair and nail strengthener but there is not sufficient evidence to support this. Biotin is normally rapidly absorbed with a serum half-life of 15 hours.
BUPRENORPHINE
Buprenorphine is a semisynthetic opioid analgesic derived from thebaine, a component of opium. It has a longer duration of action than morphine when indicated for the treatment of moderate to severe pain, peri-operative analgesia, and opioid dependence. Low doses buprenorphine produces sufficient agonist effect to enable opioid-addicted individuals to discontinue the misuse of opioids without experiencing withdrawal symptoms. Buprenorphine carries a lower risk of abuse, addiction, and side effects compared to full opioid agonists because of the “ceiling effect”, which means no longer continue to increase with further increases in dose when reaching a plateau at moderate doses.
CAFFEINE
Caffeine has been approved by the FDA since 1958 and is an everyday part of most people’s diet. It acts as a nervous system stimulant and increases alertness. It works by acting as an antagonist at the adenosine receptors and by facilitating dopamine D2 receptor transmission. Caffeine can freely cross the blood brain barrier and the placental barrier. The plasma half-life in adults is 2-8 hours and is metabolized by hepatic enzymes. Children gain these enzymes as they grow, thus caffeine can be toxic to very young children.
CARISOPRODOL
Carisoprodol, commonly known as Soma, was approved by the FDA in 1959 and used short-term to relieve the painful effects of muscle spasms. Carisoprodol has the same abuse potential and addiction symptoms to other sedatives (e.g., benzodiazepines). Carisoprodol works as a skeletal muscle relaxant by acting on the central nervous system. It has a terminal elimination half-life of approximately 2 hours. Healstone is currently able to monitor the amount of carisoprodol within 1.5 hours after ingestion. The metabolite of carisoprodol (meprobamate) is eliminated in approximately 10 hours and requires a different assay.
CATHINONE
Cathinone is currently legal in certain jurisdictions but illegal in others. The DEA of the US has designated methcathinone as a schedule I illegal drug. Cathinone is used for its euphoric effects and is a biosynthetic precursor in the synthesis of cathine. Synthetic cathinones (bath salts) are derived from natural cathinone in the khat plants. Individuals who use synthetic cathinone often report a high dependency of the drug and methamphetamine like withdrawals at a lower intensity. Cathinone has strong affinities for the dopamine transporter and norepinephrine transporter, to act as a CNS stimulant. When cathinone is chewed, elimination from the central compartment had a terminal half life of around 1.5 hours.
COCAINE
The coca plant was first chewed by the indigenous people of South America. In the 1800s, cocaine started being used in medicine as a surgical anesthetic and in other commercial products. In 1914, the Harrison Narcotics Act outlawed the sale and use of coca and opium products. Cocaine causes its addictive effects via the brain’s limbic system. Repeated long term use of cocaine rewires the reward circuity in the user’s brain and promotes addiction by requiring users to take stronger and more frequent doses to feel the same ‘high’ they initially did and for relief from withdrawal symptoms. Cocaine acts as a CNS stimulant that blocks the dopamine transporter protein and thus prolongs the amount of dopamine accumulating in the synaptic cleft. The half-life of cocaine is only 0.7-1.5 hours, with only 1% excreted unchanged in the urine. Cocaine metabolites are more detectable in urine, with benzoylecgonine detectable from within 4 hours to up to 8 days after cocaine intake.
CODEINE (OPIOID)
Codeine was originally approved in 1950 in the states as an opioid analgesic used to relieve mild to moderate pain. Taking codeine long term will cause your body to develop tolerance to the effects of codeine and require a larger intake to function. Long term use of codeine is also habit forming and can lead to withdrawal symptoms if the drug is no longer available. Codeine is metabolized to morphine and then binds with opioid receptors to alter the processing of pain perception and the emotional response. The half-lives of codeine and its metabolites have been reported to be 3 hours with majority of its excretion products found in urine within 6 hours after ingestion.
COTININE (NICOTINE)
Cigarettes were first introduced in the US in the early 19th century. The main component of a cigarette that caused its addictive properties was nicotine. Nicotine is metabolized to cotinine in the body and acts as both a sedative and a stimulant. Regular use of nicotine leads to difficult withdrawal symptoms. The American Heart Association states that nicotine consumed from smoking is one of the hardest substance to quit. Nicotine acts on the body by stimulating adrenal glands and releasing adrenaline. The metabolite cotinine has a much longer half life than nicotine and can be detected for several days after the use of tobacco.
ETHYL GLUCURONIDE
Alcohol was first brought to America by Christopher Columbus in 1492. Alcohol is a depressant that impairs and slows both physical and psychological activity and is metabolized to ethyl glucuronide in the body. Individuals can become addicted to alcohol and form a dependency on the substance leading to severe withdrawal symptoms. Alcohol works in the brain by increasing the effects of GABA (inhibitory neurotransmitter) and thus suppresses activity of the CNS. Ethyl Glucuronide has an elimination half-life of 2-3 hours and drug tests can detect this up to 5 days after consumption.
FENTANYL (OPIOID)
Fentanyl was first used in 1963 in Europe and 1968 in the states. It was a synthetic opioid that was created to be used as a pain medication and anesthetic. It is often produced illegally and is extremely potent (100 times more potent than morphine). Fentanyl carries enormous risk for addiction and abuse. Due to its high potency, there is a large increased risk of overdose and death. Fentanyl produces strong relief of pain through activating opioid receptors in the CNS. Within 72 hours, 75% of a dose of fentanyl is excreted in urine with <7% unchanged.
GABAPENTIN
Gabapentin was approved by the FDA on October 12th 2000. It is often used with other medications to prevent and control seizures. It acts as a mild tranquilizer and is commonly used illicitly by mixing with other substances to increase the effects of the intoxicant. Gabapentin has low addictive potential but does produce withdrawal symptoms and possible psychological dependence. Gabapentin works by disrupting the calcium channel signalling and thus decreasing neurotransmitter release. Gabapentin has an elimination half-life of 5-7 hours and is excreted unchanged in urine.
K3 (AB-PINACA)
AB-Pinaca is a compound that was first identified as a component of synthetic cannabis products in Japan in 2012. AB-Pinaca acts as a potent agonist for the CB1 receptor and CB2 receptor and fully substitutes for Δ9-THC in rat discrimination studies, while being 1.5x more potent. There have been a number of reported cases of deaths and hospitalizations in relation to this synthetic cannabinoid.
KETAMINE
Ketamine is a short-acting “dissociative” anesthetic due to its ability to separate perception from sensation. It also has hallucinogenic and painkilling qualities that seem to affect people in very different ways. Ketamine is chemically related to PCP (’Angel Dust’). Ketamine is occasionally administered to people but, more commonly, is used by vets for pet surgery. Generally street K is most often diverted in liquid form from vets’ offices or medical suppliers. The primary effects of ketamine last approximately 30-45 minutes if injected, 45-60 minutes when inhaled, and 1-2 hours if used orally.
KRATOM
Kratom’s legal status is ambiguous as it largely depends on the country. Kratom is an herbal extract that comes from the Mitragyna Speciosa tree in Southeast Asia and is often marketed as a treatment for muscle pain, appetite suppressant, and to stop cramps and diarrhea. People who use kratom may begin to have cravings and require treatments used for opioid addiction. Kratom is also believed to act on opioid receptors. At low doses, kratom functions as a stimulant but at high doses it acts as a sedative. Kratom’s half-life is around 23 hours with most of it excreted as metabolites in urine. The active ingredient in Kratom, Mitragynine, can be detected up to 9 days after use with a urine test.
LSD (LYSERGIC ACID DIETHYLAMIDE)
LSD was made illegal in October of 1968. LSD is a long-lasting psychoactive drug that alters the user’s perception and sensations. Users gain tolerance to LSD very quickly and must progressively take higher doses to achieve the previous level of ‘high’. This is dangerous as the increased dosage increases the chance of negative psychological effects. LSD binds to dopaminergic and serotonergic receptors to induce its psychoactive effects. The effects normally last 6-12 hours with an elimination half-life of 3 hours. Only 1% of the drug was eliminated in urine unchanged whereas 13% was eliminated as the major metabolite within 24 hours.
MEPHEDRONE
Mephedrone, also known as 4-methylmethcthinone, is a stimulant drug and New Psychoactive Substance (NPS), designed to produce effects comparable to recognized illicit drugs. It is of the amphetamine and cathinone classes and has no medicinal use. Mephedrone is most commonly ingested, either mixed in liquid or wrapped in paper. Mephedrone was classified as a Schedule I drug by the US FDA in 2012 and was made illegal in the EU in 2010.
METHADONE (OPIOID)
Methadone was approved in 1947 for analgesic and antitussive purpose and approved in 1972 by the FDA for treating opiate addiction. Methadone is still a powerful opiate with potential addictive qualities and must be closely monitored when prescribed to a patient for opioid dependency. Methadone works the same as other opioids by binding opioid receptors to exert its effects. The elimination half life is highly variable and can range from 8 to 59 hours.
METHAMPHETAMINES
In 1970, the US government banned methamphetamines for most uses. Methamphetamine is a potent CNS stimulant mainly used recreationally for the ‘high’ it provides. Methamphetamine is highly addictive and can cause addiction with even one use in certain people. Increased use of methamphetamine builds up tolerance and requires the individual to increase the dosage and frequency of the drug. Methamphetamine increases the level of dopamine/serotonin/norepinephrine by increasing release of these neurotransmitters from the nerve endings. Methamphetamine has an average half life of 5-30 hours depending on the method of administration. 30-50% of the dose is excreted unchanged in the urine of the user.
METHAQUALONE
Methaqualone (Quaalude, Sopor) is a quinazoline derivative that was first synthesized in 1951 and found clinically effective as a sedative and hypnotic in 1956. It soon gained popularity as a drug of abuse and in 1984 was removed from the US market due to extensive misuse. It is occasionally encountered in illicit form and is also available in European countries in combination with diphenhydramine (Mandrax). Methaqualone is extensively metabolized in vivo principally by hydroxylation at every possible position on the molecule. At least 12 metabolites have been identified in the urine.
METHYLENEDIOXYMETHAMPHETAMINE
In 1985, the DEA declared MDMA a schedule I drug, which it has remained since then. MDMA is a psychoactive drug mainly used for recreational purposes. No definitive research has been done on MDMA addiction; however, it affects many of the same neurotransmitter systems that addictive drugs target. MDMA acts on transporters in the brain to increase the net release of neurotransmitters. MDMA is readily absorbed from the gastrointestinal tract and has an elimination half life of 7 hours. MDMA is metabolized in the liver to an active metabolite with a longer half life of around 16-38 hours.
MORPHINE (OPIOID)
The US congress first banned opium in 1905. Morphine is an opioid drug used to relieve moderate to severe short-term pain, in other words an analgesic. Morphine has a high addiction potential due to users developing a tolerance to the drug and its pleasurable effects. It works by binding to opioid receptors and blocking the transmission of pain signals. Morphine has a half-life of 2-3 hours with 70-80% of an administered dose excreted within 48 hours. 2-10% of morphine is unchanged and recovered in urine.
OXYCODONE (OPIOID)
The FDA has banned all generic versions of the original oxycodone formula. Oxycodone is a prescription opioid pain-relieving medication used to relieve moderate to severe pain. Oxycodone can induce opioid addiction through the rush of dopamine in the brain. It acts on opioid receptors to disrupt the transmission of pain and causes euphoric effects through the release of dopamine. Studies have reported a mean terminal half life of approximately 4.5-6.5 hours. Approximately 8%-14% of the dose is excreted as free oxycodone over 24 hours after administration.
PHENCYCLIDINE
Phencyclidine, also known as PCP or Angel Dust, is a hallucinogen that was first marketed as a surgical anesthetic in the 1950’s. It was removed from the market because patients receiving it became delirious and experienced hallucinations. Phencyclidine is most commonly administered by inhalation but can be used intravenously, intra-nasally, and orally. After low doses, the user thinks and acts swiftly and experiences mood swings from euphoria to depression. PCP can be found in urine within 4 to 6 hours after use and will remain in urine for 7 to 14 days, depending on factors such as metabolic rate, user’s age, weight, activity, and diet. Phencyclidine is excreted in the urine as an unchanged drug (4% to 19%) and conjugated metabolites (25% to 30%).
PHENYTOIN
Phenytoin (also known as Dilantin) was first approved by the FDA in 1998 and is used to control and prevent certain types of seizures. Oftentimes, individuals will abuse phenytoin by taking it with other substances (most commonly alcohol) or it is added as an adulterant in cocaine. Phenytoin is believed to protect against seizures by blocking voltage gated sodium channels. This blocks the high frequency of action potentials being fired during certain seizures. The half life of phenytoin can range from 7-42 hours depending on the route of administration. The majority of phenytoin is excreted in bile with 1-5% eliminated unchanged in urine.
SECOBARBITAL (BARBITURATES)
Secobarbital was approved by the FDA in 1950 and is indicated for treatment of epilepsy, insomnia, or preoperative medication to produce anaesthesia and anxiolysis. Secobarbital and other barbiturates have a high potential for abuse and the development of physical dependence. It acts at GABA receptors to increase the inhibitory effect thus causing anesthesia/anxiolysis/etc. The half life is around 29 hours with around 5% of an oral hypnotic dose of secobarbital excreted in urine unchanged.
SYNTHETIC CANNABINOIDS
In 2012, a law was passed in the states banning substances found in synthetic marijuana. Synthetic cannabinoids are manmade chemicals marketed as a “safer” alternative to regular marijuana. The chemicals are manufactured to produce similar side effects to THC but can lead to very toxic side effects due to the lack of regulation in the production. Normal drug tests often don’t test for synthetic marijuana and individuals may choose to use synthetic cannabinoids to avoid testing positive. Continued use may lead to a psychological and physical addiction. The pharmacodynamics and pharmacokinetics vary depending on the type of synthetic cannabinoids. Not much research has been done on all the different compounds available.
TETRAHYDROCANNABINOL (THC)
Cannabis was legalized in Canada in 2018 while various states in the US have also legalized in cannabis. Marijuana used in a medical context can help treat a number of conditions. Recreational marijuana use is to pursue the ‘high’ and psychoactive symptoms that marijuana provides. There is little to no risk of marijuana overdose, however, prolonged usage of marijuana can cause the user’s brain to get reprogrammed and experience withdrawal symptoms. The active component of marijuana is THC, THC interacts with cannabinoids receptors in the brain of the user and result in inhibition of neurotransmitter release creating the effects that THC is typically known for. THC is metabolized and then oxidized to THC-COOH in the body. THC-COOH can be detected in the urine of the user within 3 days after a single use to almost 30 days in heavy chronic users.
TRAMADOL
Tramadol was approved by the FDA in 1995 as an analgesic to relieve moderate to moderately severe pain. It is generally considered as a medicine with low abuse potential relative to morphine. However, there is growing evidence of abuse in some African and West Asian countries. Tramadol works by acting on receptors to stop the transmission of pain to the brain. The elimination half life is approximately 6 hours with around 30% of an oral dose excreted unchanged in urine. Tramadol is detectable in urine for 24-72 hours after it was taken.
TRICYCLIC ANTIDEPRESSANTS
Imipramine was first approved in 1959 by the FDA which established the category of Tricyclic Antidepressants (TCA). This class of drug is used to help elevate mood and relieve depression but have largely been phased out for Selective Serotonin Reuptake Inhibitors (SSRIs). Individuals have been reported to misuse TCA by taking larger doses than prescribed to produce a ‘high’. Taking TCA can also cause dependency on the drug in certain individuals. Majority of TCA work by blocking the serotonin transporter and the norepinephrine transporter which increases the number of neurotransmitters in the synapse. The half life averages to around 1 day and can be detected up to 5 days after consumption.